MILD OVARIAN STIMULATION WITH LOW DOSE R-FSH MAY BE AN EFFECTIVE STRATEGY FOR ENDOMETRIAL PREPARATION IN WOMEN WITH THIN ENDOMETRIUM UNDERGOING FROZEN-THAW BLASTOCYST TRANSFER IN OOCYTE DONATION PROGRAMS

Abstract

To evaluate whether low dose ovarian stimulation enhances embryo implantation potential better than exogenous estrogen supplementation in women with thin endometrium undergoing frozen-thaw transfer (FET) in oocyte donation (OD) cycles. Phase 1: Fresh blastocyst transfer in 485 OD cycles during 2018-2020. Endometrial preparation was done by conventional exogenous estrogen supplementation from day5 (protocol A). Of these, 105 women had thin endometrium (< 7 mm) on day 14. Yet, fresh transfer was done since literature reports pregnancies in endometrium as thin as 3.7 mm. However, none of these 105 women conceived. Phase 2: Subsequent FET cycle of those 105 women. They were prospectively subjected to minimal stimulation protocol of 37.5 IU of r–FSH daily from d3 till day14 (protocol B). Endometrial thickness >7 mm was achieved in 95 women and blastocyst transfer was done. The remaining 10 women where adequate endometrial thickness was not attained, did not receive embryo transfer. All women, whether undergoing protocol A or B, received luteal phase support from day14 with injection micronized progesterone (100mg daily). Sr. B-hCG was measured on day 7 of blastocyst transfer and a value >50 mIU/ml was considered as positive indicator of pregnancy. Gestational sac with positive cardiac activity at week 6 confirmed implantation. Women with thin endometrium who had undergone Protocol A (n=105) were intercompared with those following Protocol B (n=95) for clinical outcomes. Endometrial thickness on day14 in women undergoing Protocol B was significantly higher as compared to those undergoing Protocol A (9.0 ± 2.0 mm vs. 5.3 ± 1.5; p = 0.0015). The endometrial echogenicity in Protocol B was also significantly enhanced (grade 2.9 ± 0.32) as against that in Protocol A (grade 2.4 ± 0.24; p = 0.0328). Similarly, on day of blastocyst transfer, the endometrial response showed a rising trend in endometrial thickness and gradation (11 ± 1.05 mm, pattern 3.9 ± 0.2) in Protocol B compared to protocol A women (6.5.0 ± 2.0 mm; grade 3.1 ± 0.5) respectively. Sr. E2 levels on day of transfer showed raised level in Protocol B compared to Protocol A (412 ± 31.0 pg/ml vs. 315 ± 49 pg/ml; P = 0.00136). None of the 105 women had achieved pregnancy in their fresh transfer cycles using Protocol A. However, in the subsequent FET cycle using Protocol B, out of 95 cycles, 24 resulted in clinical pregnancies (Pregnancy rate 25.3%) whereas 2 were ectopic pregnancies. Administration of low dose (37.5 IU) r-FSH boosts endometrial thickness and echo-pattern and significantly enhances clinical pregnancy rates in women with thin endometrium undergoing FET blastocyst transfer in OD cycles. This protocol may be followed not just for FET but fresh OD cycles too.