Abstract
Background: Endometrial preparation is essential in frozen-thawed embryo transfer (FET) cycles. Recent studies suggested that different endometrial preparation methods may influence obstetrical complications. However, the association between hormone replacement therapy (HRT) and ovarian stimulation (OS) FET endometrial preparation and obstetrical complications remains unknown.Methods: This retrospective cohort study included a total of 79,662 confirmed embryo transfer cycles during the period from January 2003 to December 2019. After exclusion, the remaining cases were categorized into an ovarian stimulation FET group (OS FET group, n = 29,121) and a hormone replacement therapy FET group (HRT FET group, n = 26,776) and subjected to the analyses. The primary outcome was the rate of obstetrical complications included placenta previa, placenta abruption, hypertensive disorders of pregnancy (HDP), placenta accreta, gestational diabetes mellitus (GDM), preterm premature rupture of the membrane (pPROM). The secondary outcome was pregnancy outcomes such as live birth rate, birth weight, pre-term and post-term delivery and cesarean sections. In order to minimize the bias, 10 pregnancy-related factors were adjusted in multiple logistic regression analysis.Results: Placenta previa (0.6 vs. 1.2%, P < 0.001) and HDP (3.5 vs. 5.3%, P < 0.001) were found lower in the OS FET than HRT FET group. Cesarean section was observed lower in the OS than HRT group (76.3 vs. 84.3%, P < 0.001). After adjustment for 10 important pregnancy-related confounding factors, we found that the risk of placenta previa (aOR 0.54, 95% CI 0.39–0.73) and HDP (aOR 0.65, 95% CI 0.57–0.75) and cesarean section (aOR 0.61, 95% CI 0.57–0.66) were still significantly reduced in the OS than HRT group. Furthermore, live birth rates were higher (80.0 vs. 76.0%, P < 0.001), and the miscarriage rate was lower (17.7 vs. 21.3%, P < 0.001) for pregnancies conceived with OS FET than with HRT FET. And the average birth weight was lower in the OS group compared to HRT group (2982.3 ± 636.4 vs. 3025.0 ± 659.0, P < 0.001), as well as the small-for-gestational age (SGA) was higher (8.7 vs. 7.2%, P < 0.001) and the large-for-gestational age (LGA) was lower (7.2 vs. 8.6%, P < 0.001) in the OS group than in the HRT group.Conclusions: The risks of placenta previa and HDP were lower in patients conceiving after OS FET than in those after HRT FET. Further prospective studies are required to further clarify the mechanism underlying the association between endometrium preparation and obstetrical complications.
Highlights
Frozen-thawed embryo transfer (FET) was well recognized to be more efficient by reducing the waste of embryos and repeated oocyte retrieval
Live birth rates were higher (80.0 vs. 76.0%, P < 0.001), and the miscarriage rate was lower (17.7 vs. 21.3%, P < 0.001) for pregnancies conceived with ovarian stimulation (OS) FET than those conceived with hormone replacement therapy (HRT) FET
Through the logistic regression model, in crude analyses, we found that the risk of cesarean section, placenta previa and hypertensive disorders of pregnancy (HDP) were significantly reduced in OS FET group than in HRT group (Table 3)
Summary
Frozen-thawed embryo transfer (FET) was well recognized to be more efficient by reducing the waste of embryos and repeated oocyte retrieval. Different cycle protocols are used for the preparation of the endometrium during FET: natural, artificial and ovarian stimulated cycles. An artificial cycle is a hormone-replacement cycle where endometrium is prepared with exogenous oestrogen followed by progesterone administration before embryo transfer, and in stimulated cycles, the follicular development is induced and controlled via gonadotropins and ovulation is triggered once the ovulation criteria are met. While several studies have investigated the rates of pregnancy, live birth, or miscarriage, the results remain controversial, and the best method of preparing the endometrium for embryo transfer remains unknown [7,8,9]. Endometrial preparation is essential in frozen-thawed embryo transfer (FET) cycles. Recent studies suggested that different endometrial preparation methods may influence obstetrical complications. The association between hormone replacement therapy (HRT) and ovarian stimulation (OS) FET endometrial preparation and obstetrical complications remains unknown
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