Transfer of cryopreserved-thawed pre-embryos in a cycle using exogenous steroids without prior gonadotrophin-releasing hormone agonist suppression yields favourable pregnancy results

Abstract

We have analysed the use of a programmed cycle of administration of exogenous steroids without prior suppression with a gonadotrophin-releasing hormone agonist (GnRHa) for the transfer of cryopreserved-thawed pre-embryos. From July 1992 to June 1994, 199 cycles (162 patients) were studied. Pre-embryos had been previously cryopreserved at the pronuclear stage using 1.5 M 1,2-propanediol as a cryoprotectant. Preparation of the endometrium was achieved in a step-up regime with transdermal oestradiol patches (0.1 to 0.4 mg). Progesterone in oil (50 mg i.m.) was started on cycle day 13. Pre-embryos were thawed on day 14 and transferred on day 15 after evidence of survival and cleavage. The mean (+/- SD) age of patients undergoing transfer was 35.4 +/- 4.3 years. The mean number of pre-embryos thawed was 4.7 +/- 1.8 with a mean of 3.3 +/- 1.4 pre-embryos being transferred. Eight of the cycles demonstrated follicular development >16 mm prior to thaw and transfer; however, these patients did not demonstrate a luteinizing hormone surge. Mean endometrial thickness on day 13 was 10.8 +/- 2.1 mm. Overall pregnancy rate was 29.2% (57/195). The ongoing or delivery rate was 16.1% (32/195). The rate of preclinical losses per transfer was 6.2% (12/195). Overall, the implantation rate was 6.2% (47/757). Thus, the use of a programmed cycle for cryopreserved embryo transfer yields favourable pregnancy outcome and offers practical advantages to patients. Prior suppression with a GnRHa is not necessary for endometrial preparation.

The endometrial preparation for frozen-thawed euploid blastocyst transfer: a prospective randomized trial comparing clinical results from natural modified cycle and exogenous hormone stimulation with GnRH agonist

“…Three retrospective papers have shown equivalent ongoing pregnancy and live birth rates between NC or modified-NC and AC with GnRH-agonist [28,30,52]. Other three papers have shown that GnRH-agonist administration is irrelevant for endometrial preparation in AC [29,53,54], counteracting a randomized controlled trial that evidenced an improved livebirth rate in AC with GnRH-agonist hormone [25,47]. Levron et al [55] showed that natural endometrium preparation yields better outcome compared with AC cycle, as demonstrated by higher implantation and clinical pregnancy rate.…”

Extended estrogen administration for women with thin endometrium in frozen-thawed in-vitro fertilization programs

“…According to Simon et al [28], transfer of frozen-thawed embryos in women with artificially prepared cycles with and without prior GnRHa suppression attributes to no difference on implantation rate as well as on endometrial thickness. Besides, Queenan et al [11] reported that the use of a programmed exogenous hormone cycle for cryopreserved embryo transfer without prior suppression with GnRHa yields favorable pregnancy outcome. Our results indicate that the programmed hormone treatment cycles can be efficiently applied by administering sequential estrogen from day 3 on without preceding GnRHa in women with thin endometrium.…”

“…Therefore, thin endometrium is an extremely poor factor that interferes with an ongoing pregnancy. Some reports suggested canceling the embryo transfer and cryopreserving all the embryos in order to avoid embryo wastage if no favorable endometrial thickness is available [6,11].…”

Intramuscular route of progesterone administration increases pregnancy rates during non-downregulated frozen embryo transfer cycles

“…This was followed by progesterone (P4) supplementation for 3 to 6 days before ET [3]. Several studies have questioned the need for GnRH analogues for the pituitary suppression of endogenous ovulation [4][5][6]. Indeed, "natural cycle override" regimens have been used in which high doses of exogenous estrogens are administered during the follicular phase of the natural cycle to prevent a premature LH surge followed by progesterone supplementation for luteal phase support when the endometrium is of adequate thickness( [7].…”