Congenital Malformations among Babies Born Following Letrozole or Clomiphene for Infertility Treatment

Sharma, Sunita; Ghosh, Sanghamitra; Singh, Soma; Chakravarty, A.; Ganesh, Ashalatha; Rajani, S.; Chakravarty, B.N.

doi:10.1371/journal.pone.0108219

Cited by 69 publications

(42 citation statements)

References 22 publications

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“…After reading the 25 remaining articles, 12 were excluded. Table S1 summarises the excluded studies and the reasons for exclusion from the final meta‐analysis …”

Section: Resultsmentioning

confidence: 99%

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Clomiphene citrate and neural tube defects: a meta‐analysis of controlled observational studies

Auffret

Cottin

Vial

et al. 2019

BJOG

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Background At the end of the 1980s, several studies suggested a potential increased risk of neural tube defects (NTDs) with ovulation induction/fertility drugs, especially with clomiphene citrate (CC). A previous meta‐analysis of observational studies evaluating the risk of NTDs associated with the use of CC performed in 1995 found a risk ratio of 1.08 (95% CI 0.76–1.51). Since then, additional studies have been published and the risk of NTDs associated with periconceptional CC exposure may have changed. Objective To perform an updated quantitative meta‐analysis of the risk of NTDs associated with periconceptional CC exposure. Search strategy MEDLINE, Web of Science, and Scopus were searched (October 2018). Selection criteria Comparative cohort and case–control studies investigating the risk of NTDs after periconceptional CC exposure. Data collection and analysis Pooled effect sizes with corresponding 95% CIs were calculated using random effects models, comparing the risk of NTDs between pregnancies exposed and not exposed to CC. Main results Thirteen studies met the inclusion criteria, totalling 218 819 pregnancies. Periconceptional exposure to CC was not significantly associated with an increased risk of NTDs (pooled odds ratio 1.21, 95% CI 0.88–1.66). No heterogeneity between studies was observed (I2 = 26%). A funnel plot and asymmetry test were not suggestive of publication bias. Conclusion Our meta‐analysis confirms that exposure to CC before or in early pregnancy was associated with a 21% increased risk of NTD in relation to CC exposure; however, this increased risk is not statistically significant. Tweetable abstract A new meta‐analysis finds that clomiphene citrate exposure before or in early pregnancy is not associated with an increased risk of NTDs.

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“…After reading the 25 remaining articles, 12 were excluded. Table S1 summarises the excluded studies and the reasons for exclusion from the final meta‐analysis …”

Section: Resultsmentioning

confidence: 99%

“…Table S1 summarises the excluded studies and the reasons for exclusion from the final meta-analysis. [14][15][16][17][18][19][20][21][22][23][24][25]…”

Section: Data Source and Selectionmentioning

confidence: 99%

Clomiphene citrate and neural tube defects: a meta‐analysis of controlled observational studies

Auffret

Cottin

Vial

et al. 2019

BJOG

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“…Even though some associations between CC use and various types of birth defects and malignancies were observed [37] , there is no conclusive evidence that CC treatment increases the risk of birth defects [10] . Letrozole was initially associated with an increased rate of cardiac and bones anomalies [38] , but many subsequent studies have since confirmed its safety [24,[39][40][41] . Most comparative studies now confirm that the anomaly rates with CC and letrozole are comparable and similar to the rates in a population of healthy women who conceive naturally [42] .…”

Section: Discussionmentioning

confidence: 99%

Clomiphene Citrate versus Letrozole for Ovarian Stimulation in Therapeutic Donor Sperm Insemination

Hachem

Antaki²,

Sylvestre³

et al. 2016

Gynecol Obstet Invest

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Aim: To compare clomiphene citrate (CC) and letrozole for ovarian stimulation (OS) in therapeutic donor sperm insemination (TDI) cycles. Methods: Retrospective cohort study between January 2011 and June 2014 at a University-affiliated private IVF clinic in Montreal, Canada. 257 normo-ovulatory women ≤40 years of age with no history of infertility undergoing 590 TDI cycles in the absence of a male partner (single women and same-sex couples) or azoospermia were included. Patients received 100 mg CC daily (145 women, 321 cycles) or letrozole 5 mg daily (112 women, 269 cycles), from days 3 to 7. Only the first 3 cycles were included per patient. Our main outcome measure was cumulative live birth rates (LBR). Results: Baseline characteristics were comparable between the 2 groups. There were no differences in LBR per cycle (16.5% (53/321) vs. 11.5% (31/269), p = 0.08) and cumulative LBR (36.6% (53/145) vs. 27.7% (31/112), p = 0.13), between CC and letrozole, respectively. Multiple pregnancy rate (11.6% (8/69) vs. 8.7% (4/46), p = 0.6) and miscarriage rate (21.7 vs. 21.7%, p = 1) were also comparable between CC and letrozole, respectively. Conclusion: In normo-ovulatory women undergoing TDI, OS with CC or letrozole resulted in similar live birth and twin pregnancy rates.

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“…Hayvan modellerinde yapılmış bir çalışmada letrozolün teratojenik etkisi olduğu bildirilmiş olmasına rağmen, daha sonrasında letrozolun konjenital anomali riskinde artışa yol açtığı gösterilememiş-tir. 24 …”

Section: Aromataz İnhi̇bi̇törleri̇unclassified

First Line Agents for Ovulation Induction: Oral Agents

Fıçıcıoğlu¹,

Özcan²

2017

TJRMS

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Ö ÖZ ZE ET TBirinci basamak oral Ovulasyon indüksiyonu (OI) ajanları çoğunlukla anovulatuar hastalık ve açıklanamayan infertil grupta kullanılır. Genellikle birinci basamak tedavi olarak kullanılan oral OI ajanları Klomifen sitrat (KS), KS ile alternatif kombine rejimler ve aromataz inhibitörleridir. OI'nun amacı; gebeliğin sağlanması için ya anovulatuar grupta monofoliküler gelişimi takiben ovulasyonun sağlanması, yada ovulatuar subfertil grupta multiple foliküler gelişime bağlı olarak fekunditenin artırılmasıdır. Anovulasyon kadın subfertilitesinin yaklaşık %10-25'inde sorumludur. Anovulatuar subfertil hastalar OI ile tedavinin planlanmasından önce, Dünya Sağlık Örgütünün (WHO) anovulasyon sınıflandırmasına göre sınıflandırılmalıdırlar. KS, oral uygulanabilen, iyi tolere edilebilen, yan etkisi az, kolay ulaşılabilen ve ucuz bir ilaçtır ve WHO grup 2 anovulatuar hastalarda ilk tedavi seçeneği olarak kabul edilir. Özellikle KS'a dirençli, obez Polikistik Over Sendromu (PKOS) hastalarında KS/metformin kombinasyonu ikinci seçenek olarak akılda tutulabilir. Bu hastalarda, kilo vermek için diyet ve egzersizin metforminle kombine edilmesi tedavide başarı şansını artırabilir. Son yayınlar; PKOS'lu anovulatuar hastalarda letrozolun ovulasyon oranları ve canlı doğum oranları açısından KS'a üstün olduğunu ve daha düşük çoğul gebelik ve OHSS oranları ile ilişkili olduğunu ortaya koymaktadır. Fakat PKOS'lu hastalar için OI açısından letrozolun ilk tedavi ajanı olarak önerilmesi için daha fazla veriye ihtiyaç vardır.A An na ah h t ta ar r K Ke e l li i m me e l le er r: : Klomifen sitrat, letrozol, anovulasyon, ovulasyon indüksiyonu A AB BS S T TR RA AC CT T First line oral treatment options are mostly used for the management of anovulatory disorder and unexplained infertility. They generally include Clomiphene citrate (CC), CC plus adjunctive treatment regimens and Aromatase inhibitors (AI). The goal of ovulation induction (OI) is either to provide a pregnancy with monofolliculer development following by ovulation in anovulatory disorder or to enhance montly chance of conception by providing multiple ovulation in unexplained infertility. Anovulatory dysfunction is responsible for about 15-20% of female subfertility. Subfertile patients with anovulatory dysfunction should be classified according to World Health Organization (WHO) classification of ovulatuary disorder before planning on OI treatment. CC is orally administered, very well tolerated, has few side effects, is easily available and is inexpensive and it is considered as the drug of choice for first line treatment of WHO class two anovulatory disorder. Especially in women with polycystic ovary syndrome (PCOS) who are obese or resistant to CC, CC plus metformin co-treatment can be a second-line option. In these patients, metformin combined with diet and exercise to achieve weight loss can increase the success of treatment. Several studies recently indicated that letrozole is superior to CC in terms of successful OI and live birth rate; it also results in fewer multi...

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Congenital Malformations among Babies Born Following Letrozole or Clomiphene for Infertility Treatment

Cited by 69 publications

References 22 publications

Clomiphene citrate and neural tube defects: a meta‐analysis of controlled observational studies

Clomiphene citrate and neural tube defects: a meta‐analysis of controlled observational studies

Clomiphene Citrate versus Letrozole for Ovarian Stimulation in Therapeutic Donor Sperm Insemination

First Line Agents for Ovulation Induction: Oral Agents

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