Transfer of frozen-thawed embryos in artificially prepared cycles with and without prior gonadotrophin-releasing hormone agonist suppression: a prospective randomized study

Abstract

Transfer of frozen-thawed embryos is usually carried out in a natural cycle or in a programmed cycle in which the endometrium is exogenously stimulated following down-regulation of the hypophysis. To analyse the possibility that the programmed cycle for embryo transfer can still be hormonally manipulated without the use of gonadotrophin-releasing hormone agonist (GnRHa) we have conducted a prospective randomized study that compared the outcome of frozen-thawed embryo transfer cycles using micronized 17beta-oestradiol and micronized progesterone preparations with and without the concomitant use of GnRHa. One hundred and six patients were randomly divided into two groups. In group A (53 patients) 4 mg/day of micronized 17beta-oestradiol was initiated following down-regulation of hypophysis. In group B (53 patients) oestrogen stimulation started on day 1 of the cycle without prior pituitary down-regulation using a dose of 6 mg/day for 7 days. In both groups, micronized progesterone in a dose of 900 mg/day was administered vaginally after at least 12 days of oestrogen stimulation. Embryo transfer embryo transfer took place 48-72 h thereafter according to the cryopreserved embryonic stage. Overall, none of the patients had any follicular development and only one cycle in group B had to be cancelled because of premature progesterone secretion. The two groups did not differ in age (31+/-5.6 and 31+/-5.0 years), number of embryos transferred per patient (3.4+/-1.2 and 3.3+/-1.0), and day of progesterone initiation (15+/-2.2 and 15+/-1.9 for groups A and B respectively). The endometrial thickness on the day of progesterone initiation was comparable in both groups (11 +/-1.6 and 10+/-1.6 mm for groups A and B respectively). Similarly, the pregnancy rate per embryo transfer and implantation rate in group A (26.4% and 9.5%) were comparable to those of group B (21.1% and 9%). These results indicate that programmed cycles can be successfully applied by administering a high dose of micronized 17beta-oestradiol starting on day 1 of the cycle. Compared to GnRHa programmed cycles, this approach is simpler, more convenient for both the patient and medical staff, and results in a similar success rate at a lower cost.

Preparation of endometrium for frozen embryo replacement cycles: a systematic review and meta-analysis

“…There appears to be no difference in clinical pregnancy and live birth rates when the AC with and without suppression groups are compared. Of the five studies included, four are RCTs [15,31,55,57].…”

“…In such cycles, the risk of cycle cancellation due to escape from suppression and hence premature ovulation has been reported to vary from 1.9 to 7.4 % [15,16]. A delay in estrogen initiation [66] or an insufficient estrogen dose [57] might be associated with a higher risk of such premature ovulation. An additional preventive measure to further reduce the incidence of premature progesterone rise might be the use of higher estrogen starting doses (e.g., 6 mg daily from day 1 to day 3 of the cycle onwards), to further suppress gonadotropin release and prevent the occurrence of follicular dominance and excessive LH secretion [57].…”

“…A delay in estrogen initiation [66] or an insufficient estrogen dose [57] might be associated with a higher risk of such premature ovulation. An additional preventive measure to further reduce the incidence of premature progesterone rise might be the use of higher estrogen starting doses (e.g., 6 mg daily from day 1 to day 3 of the cycle onwards), to further suppress gonadotropin release and prevent the occurrence of follicular dominance and excessive LH secretion [57]. However, in the above-mentioned large-scale retrospective case-control study encompassing 8362 fresh ET in donor cycles, employing AC with suppression, no significant difference in live birth rate was found between incremental or constant estrogen dosing [65].…”

“…A total of five studies, four RCTs [15,[55][56][57] and one retrospective cohort study [16], making a total of 1752 ET cycles, were included. …”

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].…”