Impact of uterine malformations on pregnancy and neonatal outcomes of IVF/ICSI–frozen embryo transfer

Abstract

STUDY QUESTION What is the impact of uterine malformations on reproductive and neonatal outcomes of IVF/ICSI–frozen embryo transfer? SUMMARY ANSWER Unification defective uteri are associated with poorer neonatal outcomes including higher preterm delivery rate and lower birthweight, and septate uteri are associated with worse fertility outcomes including higher miscarriage and lower live birth rates (LBRs). WHAT IS KNOWN ALREADY Several studies have investigated the negative effects of uterine malformations on pregnancy outcomes. However, an all-round and definitive conclusion has not been reached yet owing to the relatively low incidence of the disease and the heterogeneity of study populations, especially among women undergoing ART. STUDY DESIGN, SIZE, DURATION This was a retrospective cohort study including 411 women with congenital uterine anomalies and 14 936 women with a normal uterus who underwent first frozen-thawed embryo transfer cycles of IVF/ICSI from July 2008 to August 2019. We compared reproductive outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS Reproductive outcomes of women with uterine malformations were studied through three propensity score-matched comparisons (patients with bicorporeal uterus, septate uterus and hemi-uterus [bicorporeal, septate and hemi-uterus groups, respectively] along with corresponding control groups without uterine malformations). We also compared pregnancy and neonatal outcomes, and performed subgroup analysis addressing didelphus, bicornuate uteri and septate uteri before and after surgery independently. MAIN RESULTS AND THE ROLE OF CHANCE Compared to the matched control group, women with a bicorporeal uterus had a significantly lower LBR (24.4% versus 34.8%, odds ratio (OR) 0.61 [95% CI: 0.37, 1.00], P = 0.048). The incidence of miscarriage and preterm delivery was higher but not statistically significant (29.0% versus 18.1%, OR 1.85 [95% CI: 0.82, 4.19], P = 0.135; 22.6% versus 9.9%, OR 2.64 [95% CI: 1.07, 6.52], P = 0.063, respectively). In addition, the bicorporeal group had a significantly lower gestational age, higher caesarean rate and lower birthweight than bicorporeal control. Women with a septate uterus had comparable clinical pregnancy rates to controls (43.3% versus 49.9%, OR 0.77 [95% CI: 0.57, 1.04], P = 0.091), increased miscarriage rates (23.5% versus 13.0%, OR 2.05 [95% CI: 1.18, 3.58], P = 0.010) and lower LBRs (29.4% versus 42.2%, OR 0.57 [95% CI: 0.41, 0.79], P = 0.001). In both singleton and twins pregnancies, pregnancy and neonatal outcomes were comparable between women with a septate uterus and control. Women with a hemi-uterus had a tendency for lower clinical pregnancy rate (36.8% versus 42.3%, OR 0.80 [95% CI: 0.52, 1.21], P = 0.287) and LBR (29.8% versus 33.1%, OR 0.86 [95% CI: 0.55, 1.34], P = 0.502), compared to women without malformations. The incidences of miscarriage and preterm delivery, respectively, were 16.7% versus 16.6% (OR 1.01 [95% CI: 0.41, 2.47], P = 0.989), and 9.5% versus 11.4% (OR 0.82 [95% CI: 0.27, 2.51], P = 1) in women with a hemi-uterus as compared to control. LIMITATIONS, REASONS FOR CAUTION This was a single-centre, retrospective study in which neonatal data were extracted from parental questionnaires. The information on uteri septum type and surgery methods was poorly presented, with limited detail. In patients with uterine malformations, the number of babies with birth defects and twin pregnancies was relatively small, limiting the power of the study. WIDER IMPLICATIONS OF THE FINDINGS Compared to patients with a normal uterus, women with uterine malformation have poorer reproductive outcomes. Pregnant women with a uterine anomaly need to be managed as high-risk pregnancies and followed with appropriate obstetric review. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Ministry of Technology (2018YFC1003000), the Elite Team Project of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine (JY201801), Shanghai Sailing Program (21YF1423200) and the Fundamental Research Program Funding of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine (JYZZ117). B.W.M. is supported by an NHMRC Investigatorgrant (GNT1176437). B.W.M. reports consultancy (with stock options) for ObsEva. B.W.M. has received research funding from Ferring and Merck. The authors declare no other competing interests. TRIAL REGISTRATION NUMBER N/A.

Blastocyst quality and perinatal outcomes of frozen-thawed single blastocyst transfer cycles

“…The inconsistencies in the findings of the various studies in terms of perinatal outcomes may be caused by differences in inclusion and exclusion criteria, categories used to group blastocyst quality, and sample size distributions, especially the proportion of good-quality blastocysts in D6, as well as the relative subjectivity of blastocyst scoring. Pregnancy complications ( 31 ), uterine malformations ( 32 ), frozen-thawed technology ( 3 ), and different development rates from day 5 and day 6 ( 33 ), and the above-mentioned factors would all impact perinatal outcomes, including PTD. Meanwhile, another study ( 34 ) confirmed that an elevated AMH level would be an independent risk factor for PTD in overweight patients with polycystic ovary syndrome.…”

Risk Factors of Preterm Birth and Low Birth Weight in Singletons Conceived Through Frozen Embryo Transfer: A Retrospective Study

“…Our study found that high maternal age, primary infertility, low FSH level, and hormone replacement therapy (HRT) method of endometrial preparation for FET have a certain predictive value for preterm birth, while low FSH level, and HRT method of endometrial preparation for FET have a certain predictive value for low birth weight. In addition, other studies have found that other factors are associated with higher risks of preterm birth and low birth weight after FET, such as thin endometrium, 57 polycystic ovary syndrome (PCOS), 58 number of embryos transferred, 46 uterine malformation, 59 and higher estradiol level. 60 The value of multi-factor combination in predicting preterm birth and low birth weight is better than that of independent factors, which deserves our close attention.…”

“…International Journal of General Medicine 2022:15 endometrium, 57 polycystic ovary syndrome (PCOS), 58 number of embryos transferred, 46 uterine malformation, 59 and higher estradiol level. 60 The value of multi-factor combination in predicting preterm birth and low birth weight is better than that of independent factors, which deserves our close attention.…”

Impact of congenital uterine anomalies on reproductive outcomes of IVF/ICSI-embryo transfer: a retrospective study

“…Most studies have focused on only a particular type of uterine anomaly [ 7 – 9 ]. A retrospective study did rigorous work, but they focused solely on the frozen thawed embryo transfer (FET) outcomes of uterine anomaly [ 10 ], while the systematic study of fresh embryo transfer (IVF-ET) outcomes has not been studied.…”