The DOI matches its Crossref record; 231 of the 231 references it cites were found in a registry or an index; 71 of the 279 sources its claims cite were checked for support.
Recurrent MiscarriageGreen‐top Guideline No. 17
Open accessAbstract
Key recommendations: In this guideline, recurrent miscarriage has been defined as three or more first trimester miscarriages. However, clinicians are encouraged to use their clinical discretion to recommend extensive evaluation after two first trimester miscarriages, if there is a suspicion that the miscarriages are of pathological and not of sporadic nature. Women with recurrent miscarriage should be offered testing for acquired thrombophilia, particularly for lupus anticoagulant and anticardiolipin antibodies, prior to pregnancy. [Grade C] Women with second trimester miscarriage may be offered testing for Factor V Leiden, prothrombin gene mutation and protein S deficiency, ideally within a research context. [Grade C] Inherited thrombophilias have a weak association with recurrent miscarriage. Routine testing for protein C, antithrombin deficiency and methylenetetrahydrofolate reductase mutation is not recommended. [Grade C] Cytogenetic analysis should be offered on pregnancy tissue of the third and subsequent miscarriage(s) and in any second trimester miscarriage. [Grade D] Parental peripheral blood karyotyping should be offered for couples in whom testing of pregnancy tissue reports an unbalanced structural chromosomal abnormality [Grade D] or there is unsuccessful or no pregnancy tissue available for testing. [GPP] Women with recurrent miscarriage should be offered assessment for congenital uterine anomalies, ideally with 3D ultrasound. [Grade B] Women with recurrent miscarriage should be offered thyroid function tests and assessment for thyroid peroxidase (TPO) antibodies. [Grade C] Women with recurrent miscarriage should not be routinely offered immunological screening (such as HLA, cytokine and natural killer cell tests), infection screening or sperm DNA testing outside a research context. [Grade C] Women with recurrent miscarriage should be advised to maintain a BMI between 19 and 25 kg/m 2 , smoking cessation, limit alcohol consumption and limit caffeine to less than 200 mg/day. [Grade D] For women diagnosed with antiphospholipid syndrome, aspirin and heparin should be offered from a positive test until at least 34 weeks of gestation, following discussion of potential benefits versus risks. [Grade B] Aspirin and/or heparin should not be given to women with unexplained recurrent miscarriage. [Grade B] There are currently insufficient data to support the routine use of PGT‐A for couples with unexplained recurrent miscarriage, while the treatment may carry a significant cost and potential risk. [Grade C] Resection of a uterine septum should be considered for women with recurrent first or second trimester miscarriage, ideally within an appropriate audit or research context. [Grade C] Thyroxine supplementation is not routinely recommended for euthyroid women with TPO who have a history of miscarriage. [Grade A] Progestogen supplementation should be considered in women with recurrent miscarriage who present with bleeding in early pregnancy (for example 400 mg micronised vaginal progesterone twice daily at the time of bleeding until 16 weeks of gestation). [Grade B] Women with unexplained recurrent miscarriage should be offered supportive care, ideally in the setting of a dedicated recurrent miscarriage clinic. [Grade C]
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Claims the paper makes
104 No full text of the sources · 46 Sources not found · 35 Partly supported · 23 Supported · 22 No basis given · 10 Not checked yet · 7 Supported so far · 2 Couldn’t confirm · 2 Own result · 1 Not supported · 1 Own interpretation · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“with subgroup analysis showing a significantly more pronounced effect in women with three or more versus two or more prior miscarriages.196”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 1+]
What the sources say
- Disputedcites [196] 196. Haas DM, Hathaway TJ, Ramsey PS. Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiol- ogy. Cochrane Database Syst Rev. 2018;10:CD003511. sourceExperimental — accuracy not yet measured
In “Trials with placebo controls,” the review reports no evidence of a difference between the prior-miscarriage subgroups (interaction test P = 0.15). Although the estimated reduction was larger in the three-or-more group, the review does not find that the difference was statistically significant. (LLM, conf=0.94)
Checked by a reasoning model — may be wrong.
plaincorrelationaln = 2,359- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A systematic review has reported the miscarriage rates to be 11.3%, 17.0%, 28.0%, 39.6%, 47.2% and 63.9% for women with no, one, two or three, four, five and six previous miscarriages respectively.19”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2++]
What the sources say
- Partly supportedcites [19] 19. Coomarasamy A, Devall AJ, Brosens JJ, Quenby S, Stephenson MD, Sierra S, et al. Micronized vaginal progesterone to prevent miscar- riage: a critical evaluation of randomized evidence. Am J Obstet Gynecol. 2020;223(2):167-76. sourceExperimental — accuracy not yet measured
The Discussion’s “Target populations for progesterone therapy” section says miscarriage risk rises with the number of previous miscarriages, and its Figure 8 caption describes a systematic review of miscarriage outcomes by number of prior losses. The text available in our copy does not give the six quoted percentages, so their values and correspondence to the stated groups cannot be verified. (LLM, conf=0.83)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“In two studies, primary versus secondary (those with a previous live birth) recurrent miscarriage did not result in a significantly different future prognosis.20,21”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2++]
What the sources say
- Not checked — no full text of the sourcecites [20] 20. Brigham SA, Conlon C, Farquharson RG. A longitudinal study of pregnancy outcome following idiopathic recurrent miscarriage. Hum Reprod. 1999;14(11):2868-71. source
- Supportedcites [21] 21. Clifford K, Rai R, Regan L. Future pregnancy outcome in un- explained recurrent first trimester miscarriage. Hum Reprod. 1997;12(2):387-9. source
The results passage reports that a previous live birth conferred no advantage for the next pregnancy: 31% of women without a previous live birth miscarried, compared with 32% of those with one. This supports the claimed lack of a meaningful prognostic difference in this study. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“A meta-analysis has also reported increased miscarriage rates for men aged over 40 years, although far less pronounced when compared with the effect of increased maternal age.18”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2++]
What the sources say
- Supportedcites [18] 18. du Fossé NA, van der Hoorn MP, van Lith JMM, le Cessie S, Lashley EELO. Advanced paternal age is associated with an increased risk of spontaneous miscarriage: a systematic review and meta-analysis. Hum Reprod Update. 2020;26(5):650-69. source
The Results (Quantitative synthesis of paternal age effects; page unavailable) report increased miscarriage risk for fathers aged 40–44 and ≥45 years. The Results (Maternal age effects; page unavailable) report larger risk estimates for advanced maternal age, supporting the comparison, although maternal estimates were not pooled. (LLM, conf=0.87)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A large observational study found that compared with white Europeans, the odds of a sporadic miscarriage were increased in Black African and Black Caribbean women.22”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2+]
What the sources say
- Supportedcites [22] 22. Oliver-Williams CT, Steer PJ. Racial variation in the number of spon- taneous abortions before a first successful pregnancy, and effects on subsequent pregnancies. Int J Gynaecol Obstet. 2015;129(3):207-12. source
The Results report increased odds of a previous spontaneous abortion in Black African and Black Caribbean women compared with white European women. The Abstract’s Results give adjusted odds ratios of 1.20 and 1.31, respectively, in this large observational study of 196,040 women. (LLM, conf=0.91)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the meta-analysis of Ng et al. (2021) women with a BMI below 19 and above 25 kg/m 2 were at higher odds of recurrent miscarriage.31”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2++]
What the sources say
- Partly supportedcites [31] 31. Ng KYB, Cherian G, Kermack AJ, Bailey S, Macklon N, Sunkara SK, et al. Systematic review and meta-analysis of female lifestyle factors and risk of recurrent pregnancy loss. Sci Rep. 2021;11(1):7081. sourceExperimental — accuracy not yet measured
The Results (Underweight; Overweight and obesity, page not available) report higher odds of recurrent pregnancy loss in the general population for underweight women and women with BMI >25 kg/m². The paper does not give a BMI <19 cutoff for the pooled underweight finding, so that precise threshold is unsupported. It also finds no increased odds of a further miscarriage among underweight women who already have recurrent pregnancy loss. (LLM, conf=0.85)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“preliminary studies do not suggest an additional value or sensitivity in diagnosis associated with their use.40”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 5.2.1 | Acquired
What the sources say
- Partly supportedcites [40] 40. Tebo AE, Jaskowski TD, Hill HR, Branch DW. Clinical relevance of multiple antibody specificity testing in anti-phospholipid syndrome and recurrent pregnancy loss. Clin Exp Immunol. 2008;154(3):332-8. sourceExperimental — accuracy not yet measured
The Discussion says routine testing of the non-recommended aPL assays lacks clinical utility and that their overall combined sensitivity was not significantly higher than standard tests. The Results, however, report significantly higher sensitivity for these assays in the recurrent pregnancy loss group, although this came with lower specificity. The unqualified claim of no additional sensitivity therefore overstates the findings. (LLM, conf=0.86)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Similarly, there is some evidence for an association between increased caffeine intake and sporadic miscarriage.27”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2+]
What the sources say
- Partly supportedcites [27] 27. Chen LW, Wu Y, Neelakantan N, Chong MF, Pan A, van Dam RM. Maternal caffeine intake during pregnancy and risk of pregnancy loss: a categorical and dose-response meta-analysis of prospective studies. Public Health Nutr. 2016;19(7):1233-44. sourceExperimental — accuracy not yet measured
The Conclusions (p. 10) associate higher maternal caffeine intake with greater pregnancy-loss risk, and the Results (p. 7) say the conclusion remained the same after excluding studies involving stillbirth. The paper does not distinguish sporadic from recurrent miscarriage, so it supports the association with miscarriage generally but not that specific qualifier. (LLM, conf=0.83)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A review reported that approximately 50% of sporadic miscarriages are a result of fetal chromosome anomalies (pooled prevalence 49.7%; 95% CI 34.9-64.6%).”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 5.3.2 | Fetal chromosomal anomalies
What the sources say
- Partly supportedcites [52] 52. Zhu X, Li J, Zhu Y, Wang W, Wu X, Yang Y, et al. Application of chromosomal microarray analysis in products of miscarriage. Mol Cytogenet. 2018;11:44. sourceExperimental — accuracy not yet measured
The Results (Subject features and general findings; page unavailable) report genetic abnormalities in 55.3% (224/405) of the miscarriage samples, broadly supporting the ‘approximately 50%’ statement. This is a study of its own samples, not a review reporting a pooled prevalence; our copy does not report 49.7% or the stated 95% confidence interval. (LLM, conf=0.89)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A study has shown that miscarriages following assisted reproductive treatment have rates of cytogenetic anomalies similar to sporadic miscarriages (56.8% versus 53.6%; OR 1.11, 95% CI 0.71-1.73).52”
§ Recurrent Miscarriage Green-top Guideline No. 17 > Inherited thrombophilias
What the sources say
- Partly supportedcites [52] 52. Zhu X, Li J, Zhu Y, Wang W, Wu X, Yang Y, et al. Application of chromosomal microarray analysis in products of miscarriage. Mol Cytogenet. 2018;11:44. sourceExperimental — accuracy not yet measured
The Results (Genetic findings in subgroups) find no significant difference between assisted-reproduction and natural-conception samples, with an adjusted OR of 1.110 (95% CI 0.713–1.726). But the claim reverses the rates: 56.8% is for natural conception and 53.6% for assisted reproduction. The paper calls the comparator natural conception, not sporadic miscarriage. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
- Probably not a substantial claim. 5
- It may state two separate claims as one. 66
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“risk of miscarriage to be: 12-19 years, 13%; 20-24 years, 11%; 25-29 years, 12%; 30-34 years, 15%; 35-39 years, 25%; 40-44 years, 51%; and 45 or more years, 93%. 3”
§ Recurrent Miscarriage Green-top Guideline No. 17 > Environmental chemical exposure and dietary intake
What the sources say
- Partly supportedcites [3] 3. Nybo Andersen AM, Wohlfahrt J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: population based register linkage study. BMJ. 2000;320(7251):1708-12. sourceExperimental — accuracy not yet measured
The Spontaneous abortion section gives all seven age-group estimates, and the cited percentages are accurate when rounded. But the paper presents them as estimates under the assumption that only 80% of women with abortions in recognised pregnancies were hospitalised; the citing sentence omits that condition. (LLM, conf=0.88)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Its incidence increases with age and may affect between 10% and 50% of women aged 20 to 45 years respectively.3”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 2 | I N TRODUC T ION A N D BACKGROU N D EPIDE M IOLOGY
What the sources say
- Partly supportedcites [3] 3. Nybo Andersen AM, Wohlfahrt J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: population based register linkage study. BMJ. 2000;320(7251):1708-12. sourceExperimental — accuracy not yet measured
The Abstract and Spontaneous abortion section support an increase in miscarriage risk with maternal age. They do not support the stated 10%–50% range across ages 20–45: the Abstract reports 8.9% at ages 20–24 and 74.7% at age 45 or older. The study reports risk per pregnancy, not the percentage of women affected; page numbers are unavailable in our copy. (LLM, conf=0.86)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“A number of small studies have assessed dietary variables such as selenium, 33,34 vitamin D 35 and vitamin B12 36 specifically in the population with recurrent miscarriage, although no definitive or clinically altering conclusions can be drawn.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2-]
What the sources say
- Not checked — no full text of the sourcecites [33] 33. Al-Kunani AS, Knight R, Haswell SJ, Thompson JW, Lindow SW. The selenium status of women with a history of recurrent miscar- riage. BJOG. 2001;108(10):1094-7. source
- Supportedcites [34] 34. Thomas VV, Knight R, Haswell SJ, Lindow SW, van der Spuy ZM. Maternal hair selenium levels as a possible long-term nutritional indicator of recurrent pregnancy loss. BMC Womens Health. 2013;13:40. source
The Results report a small study of 24 women with recurrent pregnancy loss and 24 controls that assessed selenium-related dietary intake. The Conclusion says the study found no selenium difference between the groups and that selenium supplementation cannot be recommended without further research. This citation supports the selenium portion of the sentence; the vitamin D and B12 portions have separate citations. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [35] 35. Ota K, Dambaeva S, Han AR, Beaman K, Gilman-Sachs A, Kwak- Kim J. Vitamin D deficiency may be a risk factor for recurrent preg- nancy losses by increasing cellular immunity and autoimmunity. Hum Reprod. 2014;29(2):208-19. source
- Not checked — no full text of the sourcecites [36] 36. Creus M, Deulofeu R, Penarrubia J, Carmona F, Balasch J. Plasma homocysteine and vitamin B12 serum levels, red blood cell folate concentrations, C677T methylenetetrahydrofolate reductase gene mutation and risk of recurrent miscarriage: a case-control study in Spain. Clin Chem Lab Med. 2013;51(3):693-9. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“In a study by Franssen et al., 49 although overall the chances of parents with a balanced structural chromosome abnormality having a healthy child was found to be 83%, which was similar to the control couples (84%), the former had a higher chance of a subsequent miscarriage compared with the latter group (49% versus 30%; P < 0.01)”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2+]
What the sources say
- Supportedcites [49] 49. Franssen MT, Korevaar JC, van der Veen F, Leschot NJ, Bossuyt PM, Goddijn M. Reproductive outcome after chromosome analysis in couples with two or more miscarriages: index [corrected]-control study. BMJ. 2006;332(7544):759-63. source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Studies, however, have reported a low risk of parents with balanced translocations having a pregnancy with an unbalanced karyotype surviving into the second trimester (0.8%) or a disabled child born with an unbalanced chromosome abnormality (0.02%).49,50”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 5.3.1 | Parental chromosomal rearrangements
What the sources say
- Partly supportedcites [49] 49. Franssen MT, Korevaar JC, van der Veen F, Leschot NJ, Bossuyt PM, Goddijn M. Reproductive outcome after chromosome analysis in couples with two or more miscarriages: index [corrected]-control study. BMJ. 2006;332(7544):759-63. sourceExperimental — accuracy not yet measured
The Implications section (page unavailable) reports a low risk in carrier couples after recurrent miscarriage: 0.4% of pregnancies had an unbalanced karyotype detected prenatally and were terminated, and 0.4% resulted in severely handicapped children being born. Together these total 0.8%, but the paper does not describe that figure as the risk of survival into the second trimester; it reports 0.4%, not 0.02%, for affected children born. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [50] 50. Barber JC, Cockwell AE, Grant E, Williams S, Dunn R, Ogilvie CM. Is karyotyping couples experiencing recurrent miscarriage worth the cost? BJOG. 2010;117(7):885-8. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“miscarriage rates for parents with reciprocal translocations, inversions, Robertsonian translocations, and other types of chromosomal anomalies have been shown to be 54%, 49%, 34% and 27% respectively.49”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2+]
What the sources say
- Supportedcites [49] 49. Franssen MT, Korevaar JC, van der Veen F, Leschot NJ, Bossuyt PM, Goddijn M. Reproductive outcome after chromosome analysis in couples with two or more miscarriages: index [corrected]-control study. BMJ. 2006;332(7544):759-63. source
The Follow-up section reports the same four percentages for carrier couples who had one or more miscarriages: 54% for reciprocal translocations, 49% for inversions, 34% for Robertsonian translocations, and 27% for other abnormalities. These are percentages of couples with at least one miscarriage during follow-up, not percentages of pregnancies miscarried. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Chromosome anomalies of the pregnancy are the commonest cause of both sporadic miscarriage and recurrent miscarriage.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 5.3.2 | Fetal chromosomal anomalies
What the sources say
- Partly supportedcites [52] 52. Zhu X, Li J, Zhu Y, Wang W, Wu X, Yang Y, et al. Application of chromosomal microarray analysis in products of miscarriage. Mol Cytogenet. 2018;11:44. sourceExperimental — accuracy not yet measured
The Background calls chromosomal abnormalities of the embryo or fetus “one of the major” causes of miscarriage. It does not say they are the commonest cause, or establish that ranking separately for sporadic and recurrent miscarriage. The Discussion describes miscarriage as multifactorial and reports no difference in genetic-abnormality rates across groups with different adverse-pregnancy histories. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, women with arcuate (RR 1.98, 95% CI 1.06-3.69;five studies), septate (RR 2.95, 95% CI 1.51-5.77;five studies) and bicornuate uteri (RR 2.90, 95% CI 1.56-5.41;four studies) had a significantly increased risk of sporadic second trimester miscarriage versus controls.62”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2++]
What the sources say
- Partly supportedcites [62] 62. Venetis CA, Papadopoulos SP, Campo R, Gordts S, Tarlatzis BC, Grimbizis GF. Clinical implications of congenital uterine anoma- lies: a meta-analysis of comparative studies. Reprod Biomed Online. 2014;29(6):665-83. sourceExperimental — accuracy not yet measured
The Second-trimester spontaneous abortion section reports exactly the three relative risks, confidence intervals and study counts cited, with statistically significant increases versus controls. It measures spontaneous abortion, however, not specifically sporadic miscarriage; Table 2 includes a subgroup of women with recurrent spontaneous abortions. Page numbers are unavailable in our copy. (LLM, conf=0.87)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, women with septate (RR 2.65, 95% CI 1.39-5.06;six studies) and bicornuate uteri (RR 2.32, 95% CI 1.05-5.13;four studies) had a significantly increased risk of sporadic first trimester miscarriage versus normal controls.62”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2++]
What the sources say
- Partly supportedcites [62] 62. Venetis CA, Papadopoulos SP, Campo R, Gordts S, Tarlatzis BC, Grimbizis GF. Clinical implications of congenital uterine anoma- lies: a meta-analysis of comparative studies. Reprod Biomed Online. 2014;29(6):665-83. sourceExperimental — accuracy not yet measured
The First-trimester spontaneous abortion section reports the cited RRs and confidence intervals for septated and bicornuate uteri versus controls. It does not identify those estimates as specific to sporadic miscarriages; its population subgroup analysis also includes women with recurrent spontaneous abortions. The restriction to sporadic miscarriage is therefore unsupported. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A systematic review and meta-analysis has estimated the prevalence to be 5.5% (95% CI 3.5-8.5%) in unselected women, 8.0% (95% CI 5.3-12%) in infertile women, 13.3% (95% CI 8.9-20.0%) in women with recurrent miscarriage and 24.5% (95% CI 18.3-32.8)in women with infertility and miscarriage.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > Incidence
What the sources say
- Partly supportedcites [61] 61. Chan YY, Jayaprakasan K, Zamora J, Thornton JG, Raine-Fenning N, Coomarasamy A. The prevalence of congenital uterine anom- alies in unselected and high-risk populations: a systematic review. Hum Reprod Update. 2011;17(6):761-71. sourceExperimental — accuracy not yet measured
The Results (‘All uterine anomalies’; page unavailable) give all four prevalence estimates and confidence intervals as quoted. However, the 13.3% estimate is for women with a history of miscarriage, not specifically recurrent miscarriage. The Discussion (‘Women with miscarriage’; page unavailable) says studies varied in the number of prior miscarriages, although most investigated women with two or more. (LLM, conf=0.88)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“However, the significance of increased peripheral NK cells remains debatable, 101 as they do not appear to reflect the levels in the endometrium, 102 show an intracycle, hormonal and ethnic variability, 103 and appear not to predict subsequent miscarriage in a population of women with recurrent miscarriage.104”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2+]
What the sources say
- Supportedcites [101] 101. Vomstein K, Feil K, Strobel L, Aulitzky A, Hofer-Tollinger S, Kuon RJ, et al. Immunological Risk Factors in Recurrent Pregnancy Loss: Guidelines Versus Current State of the Art. J Clin Med. 2021;10(4):869. source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [102] 102. Laird SM, Mariee N, Wei L, Li TC. Measurements of CD56+ cells in peripheral blood and endometrium by f low cytome- try and immunohistochemical staining in situ. Hum Reprod. 2011;26(6):1331-7. source
- Not checked — no full text of the sourcecites [103] 103. Wang Q, Li TC, Wu YP, Cocksedge KA, Fu YS, Kong QY, et al. Reappraisal of peripheral NK cells in women with recurrent mis- carriage. Reprod Biomed Online. 2008;17(6):814-9. source
- Not checked — no full text of the sourcecites [104] 104. Katano K, Suzuki S, Ozaki Y, Suzumori N, Kitaori T, Sugiura- Ogasawara M. Peripheral natural killer cell activity as a predic- tor of recurrent pregnancy loss: a large cohort study. Fertil Steril. 2013;100(6):1629-34. source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“a previous cervical cone biopsy 78 or an ultrasonographically short cervix 79 appear to significantly predispose to second trimester miscarriage.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > Cervical insufficiency
What the sources say
- Could not verifycites [78] 78. Kyrgiou M, Athanasiou A, Paraskevaidi M, Mitra A, Kalliala I, Martin-Hirsch P, et al. Adverse obstetric outcomes after local treat- ment for cervical preinvasive and early invasive disease according to cone depth: systematic review and meta-analysis. BMJ. 2016;354:i3633. sourceExperimental — accuracy not yet measured
The citation is attached to the previous-cone-biopsy part of the sentence, not the short-cervix part. The Methods (Inclusion criteria and outcomes; page unavailable) say the review assessed pregnancies progressing beyond 24 weeks, and the Results (Maternal outcomes; page unavailable) report increased preterm birth after cervical treatment. Neither establishes a significant increase in second-trimester miscarriage; searches for “second trimester” and “miscarriage” found no such result in our copy. (LLM, conf=0.78)
- Not checked — no full text of the sourcecites [79] 79. Gilner J, Biggio J. Management of Short Cervix during Pregnancy: A Review. Am J Perinatol. 2016;33(3):245-52. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Women with diabetes who have high haemoglobin A1c levels in the first trimester are at risk of miscarriage and fetal malformation.80”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 5.5 | Endocrine
What the sources say
- Partly supportedcites [80] 80. Hanson U, Persson B, Thunell S. Relationship between haemoglo- bin A1C in early type 1 (insulin-dependent) diabetic pregnancy and the occurrence of spontaneous abortion and fetal malformation in Sweden. Diabetologia. 1990;33(2):100-4. sourceExperimental — accuracy not yet measured
The Abstract and the section ‘HbA1c in relation to occurrence of spontaneous abortion or malformation’ associate very elevated early-pregnancy HbA1c (at least 10.1%) with both outcomes. The study examined women with Type 1 diabetes, so it does not establish the claim for women with diabetes generally or for any level described simply as ‘high.’ (LLM, conf=0.85)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The prevalence of insulin resistance 91 and abnormal glucose tolerance test 92 appears to be increased in women with recurrent miscarriage compared with controls.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2++]
What the sources say
- Supportedcites [91] 91. Craig LB, Ke RW, Kutteh WH. Increased prevalence of insulin re- sistance in women with a history of recurrent pregnancy loss. Fertil Steril. 2002;78(3):487-90. source
The citation numbered 91 attaches to insulin resistance; the abnormal glucose tolerance test has a separate citation, 92. The Results section reports insulin resistance in 20 of 74 women with recurrent pregnancy loss (27.0%), compared with 7 of 74 matched controls (9.5%). (LLM, conf=0.94)
- Supportedcites [92] 92. Zolghadri J, Tavana Z, Kazerooni T, Soveid M, Taghieh M. Relationship between abnormal glucose tolerance test and history of previous recurrent miscarriages, and beneficial effect of met- formin in these patients: a prospective clinical study. Fertil Steril. 2008;90(3):727-30. source
Citation 92 is attached to the abnormal glucose tolerance test (GTT) portion of the sentence, not the insulin-resistance portion. Table 1 reports abnormal GTT in 29 women (17.6%) with recurrent miscarriage versus 4 controls (5.4%), with P=.017; the Discussion likewise describes a higher incidence in the recurrent-abortion group. (LLM, conf=0.93)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The time to pregnancy was similar in both groups, however they reported a reduction in miscarriage rates with PGD and of course a significant financial burden of US$7956 per patient.182”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2-]
What the sources say
- Supportedcites [182] 182. Ikuma S, Sato T, Sugiura-Ogasawara M, Nagayoshi M, Tanaka A, Takeda S. Preimplantation Genetic Diagnosis and Natural Conception: A Comparison of Live Birth Rates in Patients with Recurrent Pregnancy Loss Associated with Translocation. PloS one. 2015;10(6):e0129958. 183. 104. Iews M, Tan J, Taskin O, Alfaraj S, AbdelHafez FF, Abdellah AH, et al. Does preimplantation genetic diagnosis improve reproductive outcome in couples with recurrent pregnancy loss owing to struc- tural chromosomal rearrangement? A systematic review Reprod Biomed Online. 2018;36(6):677-85. source
The Results report similar intervals to a successful pregnancy in the two groups (12.4 versus 11.4 months) and significantly fewer further miscarriages with PGD. Table 4 in the Results lists a PGD cost of US$7,956 per patient; its note says this excludes a technical charge. No page number is available in our copy. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“However, in terms of studies in the recurrent miscarriage population, the cohort study of Bernardi et al. (2013) in women with two or more miscarriages, found no statistically significant difference in the subsequent live birth rate when comparing women with SCH versus euthyroid women, or treated and untreated women with SCH.85”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2++]
What the sources say
- Supportedcites [85] 85. Bernardi LA, Cohen RN, Stephenson MD. Impact of subclinical hy- pothyroidism in women with recurrent early pregnancy loss. Fertil Steril. 2013;100(5):1326-31. source
The paper describes an observational cohort of women with recurrent early pregnancy loss. The Subsequent Live-Birth Rates sections report no statistically significant difference in per-pregnancy or cumulative live-birth rates for either SCH versus euthyroid women or treated versus untreated women with SCH. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These include the broad inclusion criteria and the low number of subjects recruited (n = 80), despite the long duration of the trial (almost 8 years) and multiple participating sites (10 centres).187”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2-]
What the sources say
- Partly supportedcites [187] 187. Adewole AA, Kalu E, Okohue JE, Alabi CO, Ola B. Septum resection versus expectant management: paucity of good quality data. Hum Reprod. 2021;36(9):2626-7. sourceExperimental — accuracy not yet measured
In “Septum resection versus expectant management: paucity of good quality data” (page unavailable), the authors criticize the broad inclusion of patients and the small sample of 80. They describe recruitment as taking about 10 years, rather than almost 8, and identify the trial as multicentre without specifying 10 centres. (LLM, conf=0.88)
plainn = 80- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A systematic review of non-RCTs found the live birth rates to be similar between expectant management groups and PGT-A groups, with a trend for lower miscarriage rates in the latter.However, it is worth noting that all studies performed embryo biopsy on day 3 of development.184”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2-]
What the sources say
- Supportedcites [184] 184. Musters AM, Repping S, Korevaar JC, Mastenbroek S, Limpens J, van der Veen F, et al. Pregnancy outcome after preimplantation ge- netic screening or natural conception in couples with unexplained recurrent miscarriage: a systematic review of the best available evi- dence. Fertil Steril. 2011;95(6):2153-7 e3. source
The discussion (p. 3) reports similar live birth rates for preimplantation genetic screening and natural conception (35% and 42%) and says miscarriage rates may be lower after screening (9% versus 28%). The methods and results (pp. 2–3) clarify that these were indirect comparisons, not a randomized trial directly comparing the groups; the results (p. 2) also state that all screened embryos were biopsied on day 3. (LLM, conf=0.91)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
In the paper
“A similar incidence of approximately 1% is also the case for women experiencing a second trimester miscarriage, where random fetal chromosomal anomalies are significantly lower.6”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 2 | I N TRODUC T ION A N D BACKGROU N D EPIDE M IOLOGY
What the sources say
- Not checked — no full text of the sourcecites [6] 6. Wyatt PR, Owolabi T, Meier C, Huang T. Age-specific risk of fetal loss observed in a second trimester serum screening population. Am J Obstet Gynecol. 2005;192(1):240-6. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“By contrast, recurrent miscarriage has traditionally been defined as three or more miscarriages affecting approximately only 1% of women.4,5”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 2 | I N TRODUC T ION A N D BACKGROU N D EPIDE M IOLOGY
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Anti-beta-2-glycoprotein-I antibodies showed a trend towards a positive association, but this did not reach statistical significance (OR 2.12, 95% CI 0.69-6.53)”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 5.2.1 | Acquired
What the sources say
- Not matchedcites [39] 39. Opatrny L, David M, Kahn SR, Shrier I, Rey E. Association be- tween antiphospholipid antibodies and recurrent fetal loss in women without autoimmune disease: a metaanalysis. J Rheumatol. 2006;33(11):2214-21.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Methylenetatrahydrofolate reductase (MTHFR) mutation (heterozygous and homozygous) has been found to have a significant association with recurrent miscarriage in one meta-analysis from China.46 However other metaanalyses did not find an association and advise against testing for this mutation.41,47”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2++]
What the sources say
- Not checked — no full text of the sourcecites [46] 46. Chen H, Yang X, Lu M. Methylenetetrahydrofolate reductase gene polymorphisms and recurrent pregnancy loss in China: a systematic review and meta-analysis. Arch Gynecol Obstet. 2016;293(2):283-90. source
- Not checked — no full text of the sourcecites [41] 41. Rey E, Kahn SR, David M, Shrier I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet. 2003;361(9361):901-8. source
- Not checked — no full text of the sourcecites [47] 47. Hickey SE, Curry CJ, Toriello HV. ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing. Genet Med. 2013;15(2):153-6. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The incidence of aneuploidy in recurrent miscarriage was found to be approximately 40% (40.4%; 95% CI 25.2-55.7%),suggesting that non-genetic factors may play a more important role in recurrent miscarriage.53”
§ Recurrent Miscarriage Green-top Guideline No. 17 > Inherited thrombophilias
What the sources say
- Not checked — no full text of the sourcecites [53] 53. Zhang T, Sun Y, Chen Z, Li T. Traditional and molecular chromo- somal abnormality analysis of products of conception in sponta- neous and recurrent miscarriage. BJOG. 2018;125(4):414-20. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Protein S deficiency has not demonstrated a consistent association with recurrent first trimester miscarriage, but has shown an association with second trimester.41,44,45”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2++]
What the sources say
- Not checked — no full text of the sourcecites [41] 41. Rey E, Kahn SR, David M, Shrier I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet. 2003;361(9361):901-8. source
- Not checked — no full text of the sourcecites [44] 44. Preston FE, Rosendaal FR, Walker ID, Briet E, Berntorp E, Conard J, et al. Increased fetal loss in women with heritable thrombophilia. Lancet. 1996;348(9032):913-6. source
- Not checked — no full text of the sourcecites [45] 45. Alfirevic Z, Roberts D, Martlew V. How strong is the association between maternal thrombophilia and adverse pregnancy out- come? A systematic review. Eur J Obstet Gynecol Reprod Biol. 2002;101(1):6-14. source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The incidence of parental chromosomal rearrangements appears to be associated with recurrent miscarriage, with one large database study estimating that a translocation is present in 2.2% of parents after one miscarriage, 4.8% after two miscarriages, and 5.7% after three miscarriages.48”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 5.3.1 | Parental chromosomal rearrangements
What the sources say
- Not checked — no full text of the sourcecites [48] 48. De Braekeleer M, Dao TN. Cytogenetic studies in couples experi- encing repeated pregnancy losses. Hum Reprod. 1990;5(5):519-28. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Antithrombin deficiency is the rarer yet most thrombogenic mutation; however, the European prospective cohort study on thrombophilia (EPCOT) found only a possible association with sporadic miscarriage 44 while a subsequent meta-analysis did not.41”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2++]
What the sources say
- Not checked — no full text of the sourcecites [44] 44. Preston FE, Rosendaal FR, Walker ID, Briet E, Berntorp E, Conard J, et al. Increased fetal loss in women with heritable thrombophilia. Lancet. 1996;348(9032):913-6. source
- Not checked — no full text of the sourcecites [41] 41. Rey E, Kahn SR, David M, Shrier I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet. 2003;361(9361):901-8. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In the same study, women with intramural/subserosal myomas did not undergo surgery and experienced similar live birth rate compared with the unexplained recurrent miscarriage group in the subsequent pregnancy.70”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2++]
What the sources say
- Not checked — no full text of the sourcecites [70] 70. Saravelos SH, Yan J, Rehmani H, Li TC. The prevalence and impact of fibroids and their treatment on the outcome of pregnancy in women with recurrent miscarriage. Hum Reprod. 2011;26(12):3274-9. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Studies have shown that the higher the number of euploid miscarriages, the higher the chance of a subsequent miscarriage, 57 presumably owing to the higher chance of a persistent maternal pathology rather than a sporadic aneuploidy.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2+]
What the sources say
- Not checked — no full text of the sourcecites [57] 57. Ogasawara M, Aoki K, Okada S, Suzumori K. Embryonic karyotype of abortuses in relation to the number of previous miscarriages. Fertil Steril. 2000;73(2):300-4. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Women with submucosal myomas undergoing resection had a significant reduction in second trimester miscarriage rates (21.7% to 0%; P < 0.01), although there was a lack of a case-control group to compare what the outcome would have been if women with submucosal myomas had not undergone resection.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2++]
What the sources say
- Not checked — no full text of the sourcecites [70] 70. Saravelos SH, Yan J, Rehmani H, Li TC. The prevalence and impact of fibroids and their treatment on the outcome of pregnancy in women with recurrent miscarriage. Hum Reprod. 2011;26(12):3274-9. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A systematic review and meta-analysis has demonstrated that the incidence of intrauterine adhesions increases with the number of previous miscarriages experienced (OR 1.99, 95% CI 1.32-3.00;seven studies) and the number of previous dilatation and curettage procedures (OR 2.05, 95% CI 1.35-3.12;seven studies).73”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 3]
What the sources say
- Not checked — no full text of the sourcecites [73] 73. Hooker AB, Lemmers M, Thurkow AL, Heymans MW, Opmeer BC, Brolmann HA, et al. Systematic review and meta-analysis of intrauterine adhesions after miscarriage: prevalence, risk fac- tors and long-term reproductive outcome. Hum Reprod Update. 2014;20(2):262-78. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“However, well-controlled diabetes mellitus is not a risk factor for recurrent miscarriage, nor is treated thyroid dysfunction.81,82”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 5.5 | Endocrine
What the sources say
- Not checked — no full text of the sourcecites [81] 81. Mills JL, Simpson JL, Driscoll SG, Jovanovic-Peterson L, Van Allen M, Aarons JH, et al. Incidence of spontaneous abortion among nor- mal women and insulin-dependent diabetic women whose preg- nancies were identified within 21 days of conception. N Engl J Med. 1988;319(25):1617-23. source
- Not checked — no full text of the sourcecites [82] 82. Abalovich M, Gutierrez S, Alcaraz G, Maccallini G, Garcia A, Levalle O. Overt and subclinical hypothyroidism complicating pregnancy. Thyroid. 2002;12(1):63-8. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“More recent meta-analyses have shown an association between some cytokine gene promoter polymorphisms and recurrent miscarriage but not for others.99”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2+]
What the sources say
- Not checked — no full text of the sourcecites [99] 99. Su D, Zhang Y, Wang Q, Wang J, Jiao B, Wang G, et al. Association of interleukin-10 gene promoter polymorphisms with recurrent mis- carriage: a meta-analysis. Am J Reprod Immunol. 2016;76(2):172-80. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A meta-analysis of studies found that women with recurrent miscarriage versus controls had higher peripheral NK cell percentages (standardised mean difference [SMD] 1.36; 95% CI 0.04-2.69;P = 0.04) and higher peripheral NK cell numbers (SMD 0.81; 95% CI 0.47-1.16;P < 0.00001).100”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2+]
What the sources say
- Not checked — no full text of the sourcecites [100] 100. Seshadri S, Sunkara SK. Natural killer cells in female infertility and recurrent miscarriage: a systematic review and meta-analysis. Hum Reprod Update. 2014;20(3):429-38. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Polycystic ovary syndrome (PCOS) has been linked to an increased risk of miscarriage but the exact mechanism remains unclear.89”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2++]
What the sources say
- Not checked — no full text of the sourcecites [89] 89. Cocksedge KA, Li TC, Saravelos SH, Metwally M. A reappraisal of the role of polycystic ovary syndrome in recurrent miscarriage. Reprod Biomed Online. 2008;17(1):151-60. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, although associations between specific HLA alleles and HLA sharing with recurrent miscarriage were identified, the authors suggested that no consistent conclusions can be drawn since the observed ORs were relatively small and there was a high risk of selection and information bias present in the studies available.96”
§ Recurrent Miscarriage Green-top Guideline No. 17 > Peripheral immune factors
What the sources say
- Not checked — no full text of the sourcecites [96] 96. Meuleman T, Lashley LE, Dekkers OM, van Lith JM, Claas FH, Bloemenkamp KW. HLA associations and HLA sharing in recur- rent miscarriage: A systematic review and meta-analysis. Hum Immunol. 2015;76(5):362-73. source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Chronic endometritis has also been implicated in recurrent miscarriage, although the diagnostic criteria remain controversial.116”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2+]
What the sources say
- Not checked — no full text of the sourcecites [116] 116. Bouet PE, El Hachem H, Monceau E, Gariepy G, Kadoch IJ, Sylvestre C. Chronic endometritis in women with recurrent pregnancy loss and recurrent implantation failure: prevalence and role of office hysteroscopy and immunohistochemistry in diagnosis. Fertil Steril. 2016;105(1):106-10. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“For an infective agent to be implicated in the aetiology of recurrent miscarriage, it must be capable of persisting in the genital tract and avoiding detection or must cause insufficient symptoms to disturb the woman.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 5.7 | Infective factors
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A retrospective audit of four UK centres over periods of 5-30 years, reported that balanced translocations were found in 1.9% (406 out of 20 432) of parents with recurrent miscarriage, but only four unbalanced translocations were found after referral for prenatal diagnosis because of balanced parental translocation ascertained for recurrent miscarriage.50”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 6.2 | Genetic
What the sources say
- Not checked — no full text of the sourcecites [50] 50. Barber JC, Cockwell AE, Grant E, Williams S, Dunn R, Ogilvie CM. Is karyotyping couples experiencing recurrent miscarriage worth the cost? BJOG. 2010;117(7):885-8. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“based on which Chen et al. established a control reference range from fertile women and found that women with recurrent miscarriage did have significant increase of uterine NK cell density in precisely timed endometrial specimens.109”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 5.6.2 | Uterine
What the sources say
- Not checked — no full text of the sourcecites [109] 109. Chen X, Mariee N, Jiang L, Liu Y, Wang CC, Li TC, et al. Measurement of uterine natural killer cell percentage in the periim- plantation endometrium from fertile women and women with re- current reproductive failure: establishment of a reference range. Am J Obstet Gynecol. 2017;217(6):680:e1-6. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“A meta-analysis in couples undergoing assisted reproduction treatment showed a significant increase in miscarriage where high sperm DNA damage was identified compared with those with low DNA damage (RR 2.16; 95% CI 1.54-3.03,P < 0.00001).126”
- Also stated in: § [Evidence level 2+] · plain
“This was confirmed in a meta-analysis 2 years later.127”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2+]
What the sources say
- Not checked — no full text of the sourcecites [126] 126. Robinson L, Gallos ID, Conner SJ, Rajkhowa M, Miller D, Lewis S, et al. The effect of sperm DNA fragmentation on miscarriage rates: a sys- tematic review and meta-analysis. Hum Reprod. 2012;27(10):2908-17. source
- Not checked — no full text of the sourcecites [127] 127. Zhao J, Zhang Q, Wang Y, Li Y. Whether sperm deoxyribonucleic acid fragmentation has an effect on pregnancy and miscarriage after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis. Fertil Steril. 2014;102(4):998-1005 e8. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § [Evidence level 2+] · plain
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Retrospective studies have shown that blanket testing for parental karyotyping reveals an abnormality in less than 2%, while genetic analysis of pregnancy tissue may point towards the diagnosis.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 6.2 | Genetic
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Heparin does not cross the placenta and hence there is no potential to cause fetal haemorrhage or teratogenicity.170”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 1+]
What the sources say
- Not checked — no full text of the sourcecites [170] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“LMWH is as safe as UFH with potential advantages during pregnancy, since they cause less heparin-induced thrombocytopenia, can be administered once daily, and are associated with a lower risk of heparin-induced osteoporosis.173”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 1+]
What the sources say
- Not checked — no full text of the sourcecites [173] 173. Greer IA, Nelson-Piercy C. Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood. 2005;106(2):401-7. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Although there are concerns of potential over-diagnosis and treatment of septate uteri by using the ESHRE-ESGE classification, there are still a lack of prospective data to determine the use of which classification would lead to the most favourable reproductive outcomes (i.e. increase in live birth rate).”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2+]
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“UFH can, however, be associated with maternal complications including bleeding, hypersensitivity reactions, and heparin-induced thrombocytopenia and when used long term, osteopenia and vertebral fractures.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 1+]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Meta-analyses have shown it does not improve outcomes and may be associated with adverse effects.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2-]
boostedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“There is a lack of evidence to support routine treatment for women with Factor V Leiden, protein S deficiency and prothrombin gene mutation to reduce the incidence of recurrent miscarriage or second trimester loss.2-C Subgroup metaanalysis of RCTs do not show a consistent benefit of treatment in women with inherited thrombophilia, however the subgroups were underpowered for firm conclusions.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 1+]
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It should be noted that a meta-analysis has shown that aspirin and/or LMWH does not increase the live birth rate in women with unexplained recurrent miscarriage, may be associated with adverse effects and should therefore not be used.176”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 1+]
What the sources say
- Not checked — no full text of the sourcecites [176] 176. de Jong PG, Kaandorp S, Di Nisio M, Goddijn M, Middeldorp S. Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia. Cochrane Database Syst Rev. 2014;7:CD004734. source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“No statistically significant differences were found in the other secondary outcomes, including preterm birth (RR 1.09, 95% CI 0.71-1.66),neonatal mortality (RR 1.80, 95% CI 0.44-7.34),and fetal genital anomalies (RR 1.68, 95% CI 0.22-12.62).195”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 4]
What the sources say
- Not checked — no full text of the sourcecites [195] 195. Saccone G, Schoen C, Franasiak JM, Scott RT Jr, Berghella V. Supplementation with progestogens in the first trimester of preg- nancy to prevent miscarriage in women with unexplained recurrent miscarriage: a systematic review and meta-analysis of randomized, controlled trials. Fertil Steril. 2017;107(2):430-8 e3. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“An intention to treat retrospective analysis involving 112 couples choosing PGT-A and 188 couples choosing expectant management found the pregnancy rate, miscarriage rate and live birth rate to be similar between the two groups.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2-]
What the sources say
- Not checked — no full text of the sourcecites [185] 185. Murugappan G, Shahine LK, Perfetto CO, Hickok LR, Lathi RB. Intent to treat analysis of in vitro fertilization and preimplantation genetic screening versus expectant management in patients with re- current pregnancy loss. Hum Reprod. 2016;31(8):1668-74. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, there is a lack of consistently demonstrable benefit when used routinely in women with unexplained recurrent miscarriage, and there remains uncertainty about the optimal specific drug, route, timing and dose.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 1-B
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“There are currently insufficient data to support the routine use of PGT-A for couples with unexplained recurrent miscarriage, while the treatment may carry a significant cost and potential risk.2-C Observational studies have not demonstrated improved outcomes to date, both in terms of live birth rate and time to pregnancy interval.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2-]
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
None of the sources cited for this claim have been checked yet.
In the paper
“The PRISM trial reported no significant differences in live births in women presenting with bleeding in early pregnancy and receiving progesterone supplementation; however, in the subgroup analysis of women with recurrent miscarriage, a significant improvement in live birth rate was observed.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 7.4.3 | Cervical integrity
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A systematic review of non-RCTs reported similar live birth rates, time to conception rates and even miscarriage rates between natural conception and PGT-SR groups.183”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2-]
What the sources say
- Not checked — no full text of the sourcecites [183] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The PROMISE trial, the largest multicentre RCT to date, which was adequately powered and with a very low risk of bias, showed that routine progesterone supplementation did not improve the outcome.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 1-B
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“There is limited evidence regarding both the association and treatment of acquired uterine anomalies in women and people with recurrent miscarriage.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 3 D There is a lack of studies examining relevant interventions.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A systematic review and meta-analysis of ten RCTs of women with unexplained recurrent miscarriage receiving progesterone versus placebo or no treatment showed a lower risk of miscarriage (RR 0.72, 95% CI 0.53-0.97)and higher live birth rate (RR 1.07, 95% CI 1.02-1.15)respectively.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 4]
What the sources say
- Not checked — no full text of the sourcecites [195] 195. Saccone G, Schoen C, Franasiak JM, Scott RT Jr, Berghella V. Supplementation with progestogens in the first trimester of preg- nancy to prevent miscarriage in women with unexplained recurrent miscarriage: a systematic review and meta-analysis of randomized, controlled trials. Fertil Steril. 2017;107(2):430-8 e3. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The median time to pregnancy was 6.5 months in the PGT-A group and 3.0 months in the expectant management group.Although the study is limited by its retrospective non-randomised nature, the embryo biopsies were performed on day 5 of development, which better reflects routine practice today.185”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2-]
What the sources say
- Not checked — no full text of the sourcecites [185] 185. Murugappan G, Shahine LK, Perfetto CO, Hickok LR, Lathi RB. Intent to treat analysis of in vitro fertilization and preimplantation genetic screening versus expectant management in patients with re- current pregnancy loss. Hum Reprod. 2016;31(8):1668-74. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Consequently, in their healthy control group a miscarriage rate of only 3.5% was observed, reflecting a potential selection bias.200”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 1+]
What the sources say
- Not checked — no full text of the sourcecites [200] 200. Kumar A, Begum N, Prasad S, Aggarwal S, Sharma S. Oral dydro- gesterone treatment during early pregnancy to prevent recurrent pregnancy loss and its role in modulation of cytokine production: a double-blind, randomized, parallel, placebo-controlled trial. Fertil Steril. 2014;102(5):1357-63 e3. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Significant differences were observed in the former trial but not in the latter trial.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 1+]
What the sources say
- Not checked — no full text of the sourcecites [200] 200. Kumar A, Begum N, Prasad S, Aggarwal S, Sharma S. Oral dydro- gesterone treatment during early pregnancy to prevent recurrent pregnancy loss and its role in modulation of cytokine production: a double-blind, randomized, parallel, placebo-controlled trial. Fertil Steril. 2014;102(5):1357-63 e3. source
- Not checked — no full text of the sourcecites [201] 201. Coomarasamy A, Williams H, Truchanowicz E, Seed PT, Small R, Quenby S, et al. PROMISE: first-trimester progesterone therapy in women with a history of unexplained recurrent miscarriages -a ran- domised, double-blind, placebo-controlled, international multicentre trial and economic evaluation. Health Technol Assess. 2016;20(41):1-92. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Ethnicity, parity and pregnancy at the time of the survey were associated with different preferences, but female age, education level and time passed since the last miscarriage were not.211”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 4]
What the sources say
- Not checked — no full text of the sourcecites [211] 211. Musters AM, Koot YE, van den Boogaard NM, Kaaijk E, Macklon NS, van der Veen F, et al. Supportive care for women with recur- rent miscarriage: a survey to quantify women's preferences. Hum Reprod. 2013;28(2):398-405. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“• The majority of women expressed a low preference for admission to a hospital ward at the same gestational age as previous miscarriages and a low preference for bereavement therapy.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 4]
What the sources say
- Not checked — no full text of the sourcecites [211] 211. Musters AM, Koot YE, van den Boogaard NM, Kaaijk E, Macklon NS, van der Veen F, et al. Supportive care for women with recur- rent miscarriage: a survey to quantify women's preferences. Hum Reprod. 2013;28(2):398-405. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Bicornuate 62,a RR 1st trimester: 2.32 (1.05-5.13)2nd trimester: 2.90 (1.56-5.41)2++”
§ Recurrent Miscarriage Green-top Guideline No. 17 > Grades of Recommendation
What the sources say
- Not matchedcites 62,a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Factor V Leiden b OR 1 st trimester: 2.01 (1.13-3.58) 2 nd trimester: 7.83 (2.83-21.67)2++”
§ Recurrent Miscarriage Green-top Guideline No. 17 > Grades of Recommendation
What the sources say
- Not matchedcites b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Unicornate 62,a RR *1st trimester: 1.38 (0.83-2.28) *2nd trimester: 2.27 (0.64-7.96) 2++”
§ Recurrent Miscarriage Green-top Guideline No. 17 > Grades of Recommendation
What the sources say
- Not matchedcites 62,a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Didelphis 62,a RR *1st trimester: 1.13 (0.45-2.86) *2nd trimester: 1.71 (0.63-4.59) 2++”
§ Recurrent Miscarriage Green-top Guideline No. 17 > Grades of Recommendation
What the sources say
- Not matchedcites 62,a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Arcuate 62,a RR *1st trimester: 1.22 (0.87-1.72) 2nd trimester: 1.98 (1.06-3.69)2++”
§ Recurrent Miscarriage Green-top Guideline No. 17 > Grades of Recommendation
What the sources say
- Not matchedcites 62,a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Septate 62,a RR 1st trimester: 2.65 (1.39-5.06)2nd trimester: 2.95 (1.51-5.77)2++”
§ Recurrent Miscarriage Green-top Guideline No. 17 > Grades of Recommendation
What the sources say
- Not matchedcites 62,a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper relies on this without support.
There are currently insufficient data to support the routine use of PGT-A for couples with unexplained recurrent miscarriage.
“There are currently insufficient data to support the routine use of PGT-A for couples with unexplained recurrent miscarriage, while the treatment may carry a significant cost and potential risk.”
The authors state this as an assumption.
The women are age adjusted when comparing prognosis after aneuploid versus euploid miscarriage.
“This is assuming that the women are age adjusted, as an older woman with an aneuploid loss may still have a worse prognosis compared with a younger woman with a euploid loss.”
The authors state this as an assumption.
The mechanism linking inherited thrombophilias to recurrent miscarriage is thrombosis of the uteroplacental circulation.
“with the presumed mechanism being thrombosis of the uteroplacental circulation.”
The paper relies on this without support.
The true incidence of cervical insufficiency is unknown because the diagnosis is clinical.
“The true incidence of cervical insufficiency remains unknown, since the diagnosis is clinical.”
The paper relies on this without support.
There is currently no satisfactory objective test that can identify women with cervical insufficiency in the non-pregnant state.
“There is currently no satisfactory objective test that can identify women with cervical insufficiency in the non-pregnant state.”
The paper relies on this without support.
There are no data specifically examining the effect of polyps on sporadic or recurrent miscarriage.
“There are no data to our knowledge specifically examining the effect of polyps on sporadic or recurrent miscarriage.”
The paper relies on this without support.
For an infective agent to be implicated in the aetiology of recurrent miscarriage, it must be capable of persisting in the genital tract and avoiding detection or must cause insufficient symptoms to disturb the woman.
“For an infective agent to be implicated in the aetiology of recurrent miscarriage, it must be capable of persisting in the genital tract and avoiding detection or must cause insufficient symptoms to disturb the woman.”
The paper relies on this without support.
Immunotherapy is expensive and has potentially serious adverse effects including transfusion reaction, anaphylactic shock and hepatitis.
“Moreover, immunotherapy is expensive and has potentially serious adverse effects including transfusion reaction, anaphylactic shock and hepatitis.”
The paper relies on this without support.
There are no published data on the use of anti-TNF agents to improve pregnancy outcome in women with recurrent miscarriage.
“There are no published data on the use of anti-tumour necrosis factor (TNF) agents to improve pregnancy outcome in women with recurrent miscarriage.”
The paper relies on this without support.
There is a lack of studies examining relevant interventions for male factors.
“There is a lack of studies examining relevant interventions.”
The paper relies on this without support.
There is no evidence regarding women with recurrent miscarriage on endometrial scratch.
“There is no evidence regarding women with recurrent miscarriage and therefore by extrapolation of the data above endometrial scratch should not be recommended for women and people with unexplained recurrent miscarriage.”
The paper relies on this without support.
The value of psychological support in improving pregnancy outcome has not been tested in the form of an RCT.
“The value of psychological support in improving pregnancy outcome has not been tested in the form of an RCT.”
The paper relies on this without support.
A proportion of women will experience further miscarriage(s) following referral.
“A proportion of women will experience further miscarriage(s) following referral.”
The paper relies on this without support.
A significant proportion of cases of recurrent miscarriage remain unexplained, despite detailed investigation.
“A significant proportion of cases of recurrent miscarriage remain unexplained, despite detailed investigation.”
The paper relies on this without support.
There is no evidence to recommend treatments for male factors.
“There is no evidence to recommend treatments for male factors.”
The paper relies on this without support.
To date, there is a paucity of studies available evaluating interventions that may improve the outcome of couples with recurrent miscarriage, in particular through reducing sperm DNA fragmentation, which has been implicated in miscarriage.
“To date, there is a paucity of studies available evaluating interventions that may improve the outcome of couples with recurrent miscarriage, in particular through reducing sperm DNA fragmentation, which has been implicated in miscarriage.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
“up to 59.4% (1106/2389)”
§ Recurrent Miscarriage Green-top Guideline No. 17 > [Evidence level 2++]
Reported 59.4 · recomputed 46.295521
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“balanced translocations were found in 1.9% (406 out of 20 432) of parents with recurrent miscarriage”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 6.2 | Genetic
Reported 1.9 · recomputed 1.987079
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Recurrent Miscarriage Green-top Guideline No. 17 > 7.4.3 | Cervical integrity
“There were insufficient data to perform a subgroup analysis for women with recurrent miscarriage but the ongoing 'T4-Life' study (RCT) will examine this group.”
§ Recurrent Miscarriage Green-top Guideline No. 17 > 1-B
“found no difference between the two groups, including subgroup analysis of women with recurrent miscarriage.”
Cited works that were retracted
Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
“10.1016/j.fertnstert.2014.07.1251”
Cited work 10.1016/j.fertnstert.2014.07.1251 · retracted 2023-02-28 · notice 10.1016/j.fertnstert.2023.02.001 · this paper published 2023-06-19
A note, not an issue: for example, a cited work that was retracted only after this paper was published, which its authors could not have known.
In the paper
“2020, Statement of Retraction: Peri‐conceptional progesterone treatment in women with unexplained recurrent miscarriage: a randomized double‐blind placebo‐controlled trial, J Matern Fetal Neonatal Med, 33, 1073, 10.1080/14767058.2019.1703527”
Cited work 10.1080/14767058.2019.1703527 · retraction date not known · this paper published 2023-06-19
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Jiang, Y., Wang, L., Wang, B., Shen, H., Wu, J., He, J., Liu, A., Wang, Y., Zhang, X., & Ma, B. (2023) · American Journal of Obstetrics & Gynecology MFM · doi:10.1016/j.ajogmf.2022.100762 · Cited by 27
Recurrent early pregnancy loss and consanguinity in Omani couples
GOWRI, V., UDAYAKUMAR, A. M., BSISO, W., AL FARSI, Y., & RAO, K. (2011) · Acta Obstetricia et Gynecologica Scandinavica · doi:10.1111/j.1600-0412.2011.01200.x · Cited by 21
Lescoat, D., Jouan, H., Loeuillet-Olivo, L., & Le Calvé, M. (2005) · Prenatal Diagnosis · doi:10.1002/pd.1132 · Cited by 21
Research works printed but not linked: 3
- Regan L, 2001, Infection and pregnancy loss
- 10.1016/j.fertnstert.2009.03.021 · DOI · Paper page
- Rikken JFW, 2021, Reply: Septum resection versus expectant management: paucity of good quality data, Hum Reprod, 36, 2627
Cited by
Sorted by citations
Guidelines on the investigation and management of antiphospholipid syndrome
Arachchillage, D. J., Platton, S., Hickey, K. P., Chu, J., Pickering, M. C., Sommerville, P., MacCallum, P., & Breen, K. A. (2024) · British Journal of Haematology · doi:10.1111/bjh.19635 · Cited by 77
“165 It is well recognised that testing for APS can be affected by pregnancy itself and that testing should be performed between pregnancies wherever possible.”
Genetic causes of sporadic and recurrent miscarriage
Melo, P., Dhillon‐Smith, R. K., Islam, M. A., Devall, A., & Coomarasamy, A. (2023) · Fertility and Sterility · doi:10.1016/j.fertnstert.2023.08.952 · Cited by 65
Evaluation of Recurrent Pregnancy Loss
de Assis, V., Schenone, C. V., & Ros, S. T. (2024) · Obstetrics and Gynecology · doi:10.1097/aog.0000000000005498 · Cited by 46
“17”
Busnelli, A., Barbaro, G., Pozzati, F., D’Ippolito, S., Cristodoro, M., Nobili, E., Scambia, G., & Simone, N. D. (2024) · Human Reproduction · doi:10.1093/humrep/deae148 · Cited by 20
Li, M., Zhou, R., Yu, D., Chen, D., & Zhao, A. (2024) · Human Reproduction · doi:10.1093/humrep/deae181 · Cited by 19
Metadata
- Authors
- Regan, L., Rai, R., Saravelos, S., Li, T., & the Royal College of Obstetricians and Gynaecologists
- Affiliations
- Royal College of Obstetricians and Gynaecologists (GB)
- Corresponding author
- Regan, Lesley
- Venue
- BJOG: An International Journal of Obstetrics & Gynaecology
- Publisher
- Wiley
- Published
- 2023-06-19
- Volume
- 130
- Issue
- 12
- Pages
- e9-e39
- ISSN
- 0306-5456 (ISSN-L)
- 1470-0328
- 1471-0528
- OpenAlex
- W4381158089
- Cited by
- 158
- References
- 221
- Citations by year
- 2026: 44 · 2025: 68 · 2024: 33 · 2023: 13
- FWCI
- 17.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- BJOG An International Journal of Obstetrics & Gynaecology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Screening and Diagnostics
- Keywords
- recurrent pregnancy loss, unexplained recurrent spontaneous abortion, inherited thrombophilia, acquired thrombophilia, lupus anticoagulant, anticardiolipin antibodies, factor V Leiden, prothrombin gene mutation, protein S deficiency, cytogenetic analysis, karyology, congenital uterine anomalies, thyroid peroxidase antibodies, antiphospholipid syndrome, aspirin, heparin, preimplantation genetic testing for aneuploidy
- MeSH terms
- Abortion, Habitual, Aspirin, Female, Heparin, Humans, Male, Pregnancy, Progesterone, Semen, Antiphospholipid Syndrome, Thrombophilia
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
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