Congenital Malformations Among 911 Newborns Conceived After Infertility Treatment With Letrozole or Clomiphene Citrate

Tulandi, Togas; Martin, James S.; Al-Fadhi, Raedah; Kabli, Nadia; Forman, Rachel; Hitkari, Jason; Librach, Clifford L.; Greenblatt, Ellen; Casper, Robert F.

doi:10.1097/01.ogx.0000248776.88202.f7

Cited by 102 publications

(116 citation statements)

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“…However, this could simply be due to lack of sufficient statistical power to assess these outcomes in either of our trials (Legro et al, 2014). Our letrozole safety data are consistent with several previous studies showing no increase in fetal/neonatal anomalies in letrozole pregnancies (Tulandi et al, 2006;Legro et al, 2014).…”

supporting

confidence: 81%

Double-blind Randomized Controlled Trial of Letrozole Versus Clomiphenecitrate in Subfertile Women With Polycystic Ovarian Syndrome

Amer

Smith

Mahran

et al. 2017

Obstetrical &Amp; Gynecological Survey

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A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. SUMMARY ANSWER: Participants receiving letrozole as a primary treatment achieved a significantly (P = 0.022) higher clinical pregnancy rate per patient (61.2%) compared to CC (43.0%).WHAT IS KNOWN ALREADY: According to a recent Cochrane systematic review (2014), letrozole appears to improve live-birth (LB) and pregnancy rates in anovulatory women with PCOS, compared to CC. However, the review concluded that the quality of evidence was low due to poor reporting of study methods and possible publication bias. PARTICIPANTS/MATERIALS, SETTING, METHODS:The trial included subfertile women diagnosed with PCOS. Treatment started with one tablet (CC 50 mg, letrozole 2.5 mg) increasing to two in non-responders and continuing until pregnancy or for up to six ovulatory cycles. Non-responders were crossed over to the other treatment after a 6-week break. Cycles were initially monitored with ultrasound follicle tracking then mid-luteal serum progesterone measurement in subsequent cycles. MAIN RESULTS AND THE ROLE OF CHANCE:Amongst the 159 participants included in the intention-to-treat analysis, four women conceived before treatment and six were lost-to-follow-up. The remaining 149 participants (74 on CC and 75 on letrozole) completed at least the first treatment. Women receiving letrozole achieved a significantly (P = 0.022; absolute difference [95% confidence interval] 18% [3-33%]) higher pregnancy rate (61.%) than those on CC (43%). The median number of treatment cycles received until pregnancy was significantly (log rank P = 0.038) smaller with letrozole (4[3-5] cycles) compared to cycles). LB rates were not statistically (P = 0.089) different between the two groups, although there was a trend towards higher rates on letrozole (48.8%) compared to CC (35.4%). After the crossover, pregnancy and LB rates on letrozole (n = 45; 28.9 and 24.4%, respectively) were not statistically (P = 0.539 and P = 0.601) different from CC (n = 31; 22.6 and 19.4%). LIMITATIONS, REASONS FOR CAUTION:One possible limitation of this trial may be the exclusion of PCOS women with BMI > 35 kg/m 2 , which would limit the applicability of the results in this subgroup of PCOS. However, this group of women are generally excluded from treatment in the majority of fertility centres, especially in Europe, due to the associated challenges and risks. WIDER IMPLICATIONS OF THE FINDINGS:The results of this trial are consistent with the recent Cochrane systematic review. However, with its robust design, the current RCT provides more valid and compelling evidence for the superiority of letrozole over CC as a primary ovulation induction agent in PCOS women with 40% increase in pregnancy rates and with a shorter time-to-pregnancy. Furtherm...

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supporting

confidence: 81%

Double-blind Randomized Controlled Trial of Letrozole Versus Clomiphenecitrate in Subfertile Women With Polycystic Ovarian Syndrome

Amer

Smith

Mahran

et al. 2017

Obstetrical &Amp; Gynecological Survey

View full text Add to dashboard Cite

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“…Studies looking at foetal safety with letrozole use have found no significant difference in the rates of congenital anomalies in pregnancies conceived using letrozole, compared with clomiphene or spontaneous ovulation [38]. Side effects related to low oestrogen levels with letrozole appear to be less common than those seen with clomiphene use.…”

Section: Letrozolementioning

confidence: 93%

Fertility Treatment for Women with PCOS

Langdon¹,

Pontré²,

Hart³

2017

Testes and Ovaries - Functional and Clinical Differences and Similarities

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Polycystic ovarian syndrome is the commonest cause of anovulatory infertility. This chapter will explore fertility treatment options for this condition including the risks, benefits and success rates for different treatment methods. The importance of close patient monitoring with hormone levels and pelvic ultrasounds to ensure mono-ovulation and to avoid ovarian hyperstimulation syndrome will be highlighted.

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“…This is interesting as AIs have been promoted by some as especially advantageous in ovulation induction of the PCOS patient [2,7,10]. Even though AIs appear to be safe in terms of fetal teratogenic risks [15], Novartis, the producer of Letrozole, states that it is only indicated for postmenopausal women and it is contraindicated in women who may become pregnant (http:// www.pharma.us.novartis.com/product/pi/pdf/Femara.pdf). It is likely that many physicians are refraining from the offlabel use of Letrozole for ovulation induction.…”

Section: Discussionmentioning

confidence: 99%

Fertility management in the PCOS population: results of a web-based survey at IVF-worldwide.com

Brezina¹,

Mensah

Balen

et al. 2013

J Assist Reprod Genet

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Purpose To identify the leading treatment strategies for infertile women with PCOS on an international scale. Methods A retrospective evaluation using the results of a web-based survey, (IVF-Worldwide (www.IVF-worldwide. com), posted from 1 to 30 September 2010 was performed. Binomial confidence intervals for proportions were calculated by the modified Wald method with significance defined as P <0. 05 using a DataStar software package (DataStar, Waltham, MA, USA). Incomplete surveys were excluded from the analysis. ResultsThe results from 262 centers in 68 nations were obtained. Clomiphene citrate was the clear first choice, 68 %, for PCOS treatment in the respondent group. Eightyeight percent of respondents utilized ultrasound follicular monitoring when conducting ovulation induction with oral medications. A significant (p <0.05) proportion of respondents (66 %) did use some BMI cutoff beyond which IVF treatment was not offered. The preferred IVF protocols for PCOS patients were gonadotropin releasing hormone (GnRH) antagonist, 46 %, and GnRH agonist, 51 %. There was heterogeneity of responses observed regarding the management of a patient at very high risk of OHSS. Conclusions While some advances, such as the use of GnRH antagonist regimen in IVF cycles, were relatively underutilized, the survey gives an unfiltered snapshot at the practice patterns of a large number of clinics. Results from this survey may be used by researchers and professional organizations to improve the clinical care of PCOS women suffering with infertility.

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Congenital Malformations Among 911 Newborns Conceived After Infertility Treatment With Letrozole or Clomiphene Citrate

Cited by 102 publications

References 0 publications

Double-blind Randomized Controlled Trial of Letrozole Versus Clomiphenecitrate in Subfertile Women With Polycystic Ovarian Syndrome

Double-blind Randomized Controlled Trial of Letrozole Versus Clomiphenecitrate in Subfertile Women With Polycystic Ovarian Syndrome

Fertility Treatment for Women with PCOS

Fertility management in the PCOS population: results of a web-based survey at IVF-worldwide.com

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