Among patients with POI longer duration of endometrial stimulation needed compared with older women using donor egg embryos: Study

This was a single-center retrospective cohort study (February 2019–September 2022) at Mount Sinai Hospital, Toronto, Canada. All patients underwent programmed ET cycles. The POI group was compared with an advanced reproductive age (ARA) group (>41 years old), both undergoing fresh or frozen donor egg ET, and a control group undergoing autologous frozen ET. Estrace (4 mg twice daily) was initiated on day 2, and an ultrasound was performed on day 14. When EMT <8 mm, transdermal estradiol (100 mg) every other day was added with a reassessment in 5–7 days. Progesterone was initiated once EMT R8 mm, and luteal support depended on patient as well as physician preference. Embryo transfers were cancelled for persistently thin lining, fluid in the cavity, or uterine pathology.

The primary outcome was days to optimal EMT. Secondary outcomes included early pregnancy loss rate, clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR), and ultrasound characteristics. Subgroup analysis assessed pregnancy outcomes in patients with POI requiring >3 weeks vs. ≤3 weeks to optimal EMT.

A total of 878 cycles from 387 patients (177 cycles/51 patients with POI, 357 cycles/135 patients with ARA, and 344 cycles/ 201 controls) were included. Patients with POI required a longer time to optimal EMT compared with ARA and controls (median [interquartile range]: POI 13 days [12.0–19.0] vs. ARA 12 days [12.0– 13.3] vs. controls 12 days [12.0–13.0], P<.001). No differences were seen in early pregnancy loss rate, CPR, or OPR between groups.

Patients with POI were more likely to exhibit fluid in the cavity (POI 10.2% vs. ARA 4.2% vs. controls 3.8%, P=.004) and subendometrial cysts (POI 14.7% vs. ARA 6.2% vs. controls 4.9%, P<.001).

A higher proportion of patients with POI required >3 weeks for optimal EMT compared with ARA and controls. Within the POI group, those requiring >3 weeks had a lower CPR (>3 weeks: 20.6% vs. ≤3 weeks: 34.6%, P≤0.1) and lower OPR (>3 weeks: 5.9% vs. ≤3 weeks: 22.0%, P=0.05)

In this study, patients with POI required a longer duration of endometrial stimulation compared with older women using donor egg embryos and age-matched women using autologous embryos. In addition, in patients with POI, endometrial stimulation >3 weeks was linked to lower pregnancy outcomes. There is limited research on the effect of endometrial stimulation duration on pregnancy outcomes in the POI population. Although other studies did not show an impact with extended stimulation, some studies did not address whether a specific EMT threshold was achieved.

The response of the endometrium to estrogen stimulation may fundamentally differ in patients with POI because of a lack of endogenous hormones, and longer stimulation may reflect intrinsic differences in endometrial development. One study showed that patients with POI on prior hormone replacement therapy had a nonsignificant trend toward higher EMT and CPR. In this study, authors used EMT ≥8 mm as a threshold. Although studies have indicated EMT of 7 mm may yield comparable outcomes in nondonor egg cycles, these studies did not specifically explore the impact of EMT in POI, necessitating further research to determine whether patients with POI require a different EMT threshold. Limitations of study include small samples in our subgroup analysis; thus, caution in interpreting these results is advised. Nonetheless, clinicians should be mindful of the potential impact extended endometrial stimulation may have on pregnancy outcomes in patients with POI.

Source: Trish Dinh, Qixuan Li, Ella Huszti; FertSert VOL. 122 NO. 5 / NOVEMBER 2024

https://doi.org/10.1016/j.fertnstert.2024.06.019

Among patients with POI  longer duration of endometrial stimulation needed compared with older women using donor egg embryos and age-matched women using autologous embryos.