Letrozole-induced frozen embryo transfer cycles are associated with a lower risk of hypertensive disorders of pregnancy among women with polycystic ovary syndrome

Zhang, Jie; Wei, Mengjie; Bian, Xiaolan; Wu, Ling; Zhang, Shuo; Mao, Xiaoyan; Wang, Bian

doi:10.1016/j.ajog.2021.01.024

Cited by 31 publications

(22 citation statements)

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“…Hence, up to 35% of patients with gestational hypertension develop preeclampsia (46). Our findings of an increased risk to develop HDP are in line with a growing body of evidence accumulating from mainly observational studies examining the impact of different FET protocols on maternal and neonatal outcomes (15,16,20,(47)(48)(49)(50)(51). Previous studies report on the more frequent occurrence of LGA infants and macrosomia after programmed FET cycles (16,43,48) while we found higher birthweight and birthweight percentile after FET with CL absence as well as CL absence as a significant predictor of higher birthweight and birthweight percentiles.…”

Section: Discussionsupporting

confidence: 84%

Pregnancy Outcomes After Frozen-Thawed Embryo Transfer in the Absence of a Corpus Luteum

et al. 2021

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Background: Nowadays, frozen-thawed embryo transfer (FET) cycles represent a high proportion of fertility treatments worldwide. Recent studies suggest differences in pregnancy outcomes depending on the FET treatment protocol used. The reason for this is still unclear, but the number of corpora lutea (CL) at conception is discussed as a possible factor. This study aims to investigate whether maternal and neonatal outcomes for pregnancies following FET lacking a CL differ from FET with one or more CL in order to explore a potential link between CL absence and adverse pregnancy outcomes.Methods: The study was designed as a retrospective, multi-center observational study with two cohorts after singleton live birth [0 CL cohort (FET in a programmed cycle, n = 114) and ≥ 1 CL cohort (FET in a natural or stimulated cycle, n = 68)]. Participants completed a questionnaire on the outcome of pregnancy and birth records were analyzed in a descriptive way. Multivariable logistic and linear regressions were performed in order to explore associations between CL absence and pregnancy outcomes. The strength of the agreement between the information in the survey and the diagnoses extracted from the files was assessed by Cohen's Kappa.Results: The risk of hypertensive disorders of pregnancy was higher after FET in the absence of a CL compared to FET with CL presence (aOR 5.56, 95% CI 1.12 – 27.72). Birthweights and birthweight percentiles were significantly higher in the 0 CL group. CL absence was a predictor of higher birthweight (adjusted coefficient B 179.74, 95% CI 13.03 – 346.44) and higher birthweight percentiles (adjusted coefficient B 10.23, 95%, 95% CI 2.28 – 18.40) particularly in female newborns of the 0 CL cohort. While the strength of the agreement between the reported information in the survey and the actual diagnoses extracted from the files was good for the majority of outcomes of interest it was fair in terms of hypertension (κ = 0.38).Conclusion: This study supports observations suggesting a potential link between a lack of CL at conception and adverse maternal and neonatal outcomes. Further investigations on causes and pathophysiological relationships are yet to be conducted.

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Section: Discussionsupporting

confidence: 84%

Pregnancy Outcomes After Frozen-Thawed Embryo Transfer in the Absence of a Corpus Luteum

et al. 2021

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“…A recent meta-analysis including 4 retrospective studies with 2933 women with PCOS published from 2013 to 2019, suggested that the pregnancy outcomes, including rates of live birth, ongoing pregnancy, clinical pregnancy, implantation and miscarriage rate were not significantly different between artificial and ovarian stimulation cycles [ 12 ]. After that, 1 RCT study [ 13 ] and 4 retrospective studies [ 14 – 17 ] on the topic have been published, suggesting the therapeutic effects might be different among various ovulation stimulation regimens. Which stimulation regimen superior to HRT has yet been analyzed in the previous review paper.…”

Section: Introductionmentioning

confidence: 99%

Systematic review update and meta-analysis of randomized and non-randomized controlled trials of ovarian stimulation versus artificial cycle for endometrial preparation prior to frozen embryo transfer in women with polycystic ovary syndrome

Zhang

et al. 2022

Reprod Biol Endocrinol

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Purpose This systematic review and meta-analysis aimed to compare the short-term reproductive and long-term obstetric outcomes after endometrial preparations by ovarian stimulation protocols and hormone replacement therapy (HRT) in women with polycystic ovary syndrome (PCOS) prior to frozen embryo transfer (FET). Method PubMed, EMBASE, Web of Science and the Cochrane Library were searched to identify relevant studies. Primary outcome was live birth rate, secondary outcomes included the rates of clinical pregnancy, miscarriage, implantation and hCG-postive, cycle cancellation, ectopic pregnancy, preterm birth, preeclampsia, gestational hypertension, gestational diabetes mellitus and abnormal placentation. Results Nine studies, including 8327 patients with PCOS, were identified. Live birth rate was significantly higher (RR = 1.11, 95% CI = 1.03–1.19) and miscarriage rate (RR = 0.60, 95% CI = 0.46–0.78) was significantly lower in stimulated protocol compared to the rates in HRT. While the rates of ongoing pregnancy, clinical pregnancy, implantation, hCG-positive, cycle cancellation and ectopic pregnancy showed no significant difference between the two protocols. Compared HRT with different stimulation protocols, significantly higher clinical pregnancy rate (RR = 1.54, 95% CI = 1.20–1.98) were found in letrozole group, but not in the other subgroups. For the obstetric outcomes, the preterm birth and preeclampsia rates were significantly lower in the stimulated group compared to that in the HRT group (RR = 0.85, 95% CI = 0.74–0.98; RR = 0.57, 95% CI = 0.40–0.82, respectively), while gestational hypertension, gestational diabetes mellitus and abnormal placentation rates showed no significant difference. Conclusions The present data suggest that ovarian stimulation protocol as an endometrial preparation regimen prior to FET might be superior to HRT protocol with a significantly higher rate of live birth, lower risk of miscarriage, preterm birth and preeclampsia. Our study showed stimulated protocol is better than HRT regimen as an endometrial preparation for women with PCOS. However, quality of the evidence is low, more well-designed RCT studies are still needed to confirm the results before clinical recommendation, particularly direct comparisons between letrozole and other stimulated regimens.

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“…Some studies suggested that women with PCOS are at increased risk of PE possibly because of insulin resistance and obesity, which are more common in this population. 91 In a recent publication that included only patients with PCOS undergoing FET, 56 FET-SC was associated with a lower risk of HDP than FET-AC, suggesting that the CL may play a role in mitigating the risk of hypertensive disorders within the population with PCOS undergoing FET. The current literature does not definitively resolve the question of whether subfertility itself could modify the effect of the CL on the incidence of PE.…”

Section: Clinical Opinionmentioning

confidence: 99%

Potential role of the corpus luteum in maternal cardiovascular adaptation to pregnancy and preeclampsia risk

Conrad

Versen‐Höynck

Baker

2022

American Journal of Obstetrics and Gynecology

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Letrozole-induced frozen embryo transfer cycles are associated with a lower risk of hypertensive disorders of pregnancy among women with polycystic ovary syndrome

Cited by 31 publications

References 50 publications

Pregnancy Outcomes After Frozen-Thawed Embryo Transfer in the Absence of a Corpus Luteum

Pregnancy Outcomes After Frozen-Thawed Embryo Transfer in the Absence of a Corpus Luteum

Systematic review update and meta-analysis of randomized and non-randomized controlled trials of ovarian stimulation versus artificial cycle for endometrial preparation prior to frozen embryo transfer in women with polycystic ovary syndrome

Potential role of the corpus luteum in maternal cardiovascular adaptation to pregnancy and preeclampsia risk

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