Risks of Placenta Previa and Hypertensive Disorders of Pregnancy Are Associated With Endometrial Preparation Methods in Frozen-Thawed Embryo Transfers

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.

Pregnancy outcomes of four different cycle protocols for frozen embryo transfer: a large retrospective cohort study

“…The results showed that HRT cycles had similar possibilities of biochemical pregnancy, clinical pregnancy, abortion, and live birth compared to the natural cycles, regardless of whether day 3 cleavage stage embryos or day five or six blastocyst stage embryos were transferred. Previous studies showed that the HRT protocol was associated with an increased risk of maternal and neonatal complications [17,21] . However, we did not obtain data on pregnancy complications and neonatal outcomes because of the limitations of the retrospective collection of medical records.…”

Endometriosis does not seem to be an influencing factor of hypertensive disorders of pregnancy in IVF / ICSI cycles

“…In a big data retrospective analysis conducted in Japan, it was found that, compared with patients with natural ovulation cycle (NC-FET), patients using HRT-FET had an increased risk of HDP and placental implantation, while the risk of GDM was observed to be reduced [ 37 ]. Another retrospective cohort study in China also found that the HRT-FET group had an increased risk of HDP and placenta previa compared to ovarian stimulation in the FET group [ 14 ]. These results suggested that endometrial preparation methods may be related to obstetric complications, especially with respect to the development of HDP.…”

“…It is generally believed that the occurrence of HDP may be related to immune system disorder, trophoblast or placental ischemia and oxidative stress [ 11 , 12 ]. Studies have also shown that the incidence of HDP is higher when using assisted reproductive technology (ART), especially in the frozen-thawed embryo transfer (FET) cycle [ 13 ], which may be related to the endometrial preparation protocol in the FET cycle [ 14 ].…”

Assessing obstetric outcomes: A systematic review and meta‐analysis comparing fresh, artificial, and natural thaw embryo transfer cycles

“…8,26 Gestational diabetes GD was assessed in 17 studies, summarised below in Figure S41. 6,[9][10][11][12][13][14][15][16][17][19][20][21][22][24][25][26] The analysis comparing GD in ArtThawET and NatThawET looked at 38 821 artificial cycles and 48 828 natural cycles, showed a small but significant increase in GD in NatThawET (OR 0.94, 95% CI 0.88, 0.99). There were two studies which compared GD in ArtThawET and FreshET.…”

“…Fifteen studies evaluated PTB as an outcome -the results of these studies are summarised in Figure S40. [6][7]10,[12][13][16][17][19][20][21][22][23][26][27][28] The pooled analysis of PTB comparing ArtThawET and NatThawET included 47 585 artificial cycles and 50 970 natural cycles. The pooled estimate of PTB showed a significant result, with a higher rate of PTB in ArtThawET (OR 1.18, 95% CI 1.13, 1.23).…”