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Early pregnancy complications after frozen-thawed embryo transfer

Women who underwent a frozen-thawed embryo transfer (FET) for assisted reproductive technology (ART) treatment were nearly twice as likely to experience bleeding or miscarriage in the first trimester with hormone replacement cycles (HRC-FET) compared to natural cycles (NC-FET), according to a retrospective cohort study published in the European Journal of Obstetrics & Gynecology and Reproductive Biology.

The authors noted that FET is a key component of ART and that various cycle regimens are used worldwide, due to insufficient evidence that favors specific transfer schedules.

The study analyzed 7,342 pregnancies after FET that were registered in the Swiss IVF Registry from 2014 to 2019.

Women were divided into three groups, according to cycle regimen leading to pregnancy: NC-FET, with or without human chorionic gonadotropin (hCG) ovulation trigger(n = 998); low-dose stimulation cycles, with or without luteal phase support (SC-FET) (n = 984); and HRC-FET (n = 5,360).

The mean maternal age was 35.5, 35.6 and 35.3 years in the NC-FET, SC-FET and HRC-FET groups, respectively.

The percentage of previous recurrent miscarriages was low: 0.3% for NC; 0.3% for SC; and 0.8% for HRC (P = 0.062).

The three FET groups differed significantly, however, in the percentage of patients with chronic anovulation/polycystic ovary syndrome (PCOS) and endometriosis.

The lowest rate of chronic anovulation/PCOS and highest rate of mild endometriosis were in the NC-FET group: 5.7% and 8.1%, respectively.

By contrast, chronic anovulation/PCOS and severe endometriosis were most pronounced in the HRC-FET group: 17.6% and 5.7%, respectively.

The rates of thyroid disease were 3.4% for NC; 3.2% for SC; and 6.2% for HRC (P < 0.001). But there were no significant differences in other clinically relevant comorbidities.

The incidence of early pregnancy bleeding in the first trimester was 3.5% for NC; 4.3% for SC; and 8.4% for HRC (P < 0.001).

Similarly, the prevalence of miscarriage at less than 12 weeks was 19.0% for NC; 19.7 % for SC; and 29.1% for HRC (P < 0.001).

Multivariate analysis found almost a doubled adjusted odds ratio (aOR) for bleeding in the first trimester with HRC-FET vs. NC-FET: aOR = 1.92; 95 % confidence interval (CI):1.30 to 2.81.

Likewise, the aOR for miscarriage < 12 weeks was 1.82; 95 % CI: 1.51 to 2.19, respectively.

ORs were comparable for HRC-FET and SC-FET.

Also, no differences were observed in the outcomes between SC-FET and NC-FET.

Furthermore, the rates of late miscarriages or ectopic pregnancies were similar for the three cycle regimens.

The percentage of live births per pregnancy were 78.0 % for NC; 77.2% for SC; and 68.2% for HRC (P < 0.001).

NC-FET also achieved the highest rate of singleton deliveries: 70.5%.

“This study supports adverse early pregnancy outcomes in cycles in which the corpus luteum is suppressed,” wrote the authors.

They also noted that this is the latest large European register study to evaluate early pregnancy complications and the live birth rate per pregnancy after FET among the three different cycle regimens.

Study results indicate that “HRC-FET should be avoided and replaced by SC-FET or NC-FET to achieve better pregnancy outcomes,” wrote the authors.

Further research is needed, though, to elucidate the potential mechanism underlying the impact of FET regimens (with or without corpus luteum) on early pregnancy complications.

Reference

Pape J, Levy J, von Wolff M. Early pregnancy complications after frozen-thawed embryo transfer in different cycle regimens: a retrospective cohort study. Eur J Obstet Gynecol Reprod Biol. 2022 Dec;279:102-106. doi:10.1016/j.ejogrb.2022.10.015