Nonsupplemented Luteal Phase Characteristics after the Administration of Recombinant Human Chorionic Gonadotropin, Recombinant Luteinizing Hormone, or Gonadotropin-Releasing Hormone (GnRH) Agonist to Induce Final Oocyte Maturation inin VitroFertilization Patients after Ovarian Stimulation with Recombinant Follicle-Stimulating Hormone and GnRH Antagonist Cotreatment

Abstract

Replacing GnRH agonist cotreatment for the prevention of a premature rise in LH during ovarian stimulation for in vitro fertilization (IVF) by the late follicular phase administration of GnRH antagonist may render supplementation of the luteal phase redundant, because of the known rapid recovery of pituitary function after antagonist cessation. This randomized two-center study was performed to compare nonsupplemented luteal phase characteristics after three different strategies for inducing final oocyte maturation. Forty patients underwent ovarian stimulation using recombinant (r-)FSH (150 IU/d, fixed) combined with a GnRH antagonist (antide; 1 mg/d) during the late follicular phase. When at least one follicle above 18 mm was observed, patients were randomized to induce oocyte maturation by a single injection of either r-human (h)CG (250 microg) (n = 11), r-LH (1 mg) (n = 13), or GnRH agonist (triptorelin; 0.2 mg) (n = 15). Retrieved oocytes were fertilized by either IVF or intracytoplasmatic sperm injection, depending on sperm quality. Embryo transfer was performed 3-4 d after oocyte retrieval. No luteal support was provided. Serum concentrations of FSH, LH, estradiol (E(2)), progesterone (P), and hCG were assessed at fixed intervals during the follicular and luteal phase. The median duration of the luteal phase was 13, 10, and 9 d for the r-hCG, the r-LH, and the GnRH agonist group, respectively (P = 0.005). The median area under the curve per day (from 4 d post randomization until the onset of menses) for LH was 0.50, 2.34, and 1.07 for the r-hCG, the r-LH, and the GnRH agonist group, respectively (P = 0.001). The median area under the curve per day for P was 269 vs. 41 and 16 for the r-hCG, the r-LH, and the GnRH agonist group, respectively (P < 0.001). Low pregnancy rates (overall, 7.5%; range, 0-18% per started cycle) were observed in all groups. In conclusion, the nonsupplemented luteal phase was insufficient in all three groups. In the patients receiving r-hCG, the luteal phase was less disturbed, compared with both other groups, presumably because of prolonged clearance of hCG from the circulation and the resulting extended support of the corpus luteum. Despite high P and E(2) concentrations during the early luteal phase in all three groups, luteolysis started prematurely, presumably because of excessive negative steroid feedback resulting in suppressed pituitary LH release. Hence, support of corpus luteum function remains mandatory after ovarian stimulation for IVF with GnRH antagonist cotreatment.

Efficacy of luteal phase support with vaginal progesterone in intrauterine insemination: a systematic review and meta-analysis

“…With reference to the ART, various mechanisms have been proposed to explain the luteal deficiency observed particularly in IVF cycles, although there is some controversy in the published literature [2][3][4][5][6]. Indeed, one can assume that multifollicular development and consequently the supraphysiological estradiol levels secreted by the multiple corpora lutea during the early luteal phase exert a negative feedback of the hypothalamicpituitary axis, inhibiting the LH release necessary for the corpus luteum function [7].…”

Has ART Finally Got a Patient-Friendly Progesterone?

“…Abysmally low levels of luteal phase LH may be insufficient to promote endometrial maturation to support an early pregnancy. Endogenous LH secretion can be suppressed for as long as 10 days after GnRH agonist treatment [15,16]. In order to compensate the low levels, progesterone gel, intramuscular progesterone, and suppository forms of this steroid are used by clinicians.…”

Gonadotropin-releasing hormone-agonist induces apoptosis of human granulosa-luteal cells <i>via</i> caspase-8, -9 and -3, and poly-(ADP-ribose)-polymerase cleavage

“…It has also been reported that GnRH affects the cellular physiologic changes in the ovary, and oocyte growth and ovulation (2,3). This GnRH effect on ovarian function is associated with apoptosis in the ovary (7,8), but the mechanism has not yet been defined.…”

“…This gonadotropin affects the gonads and associated organs (1). GnRH affects the ovary directly without involving the pituitary gland; specifically, GnRH influences physiologic changes in ovarian granulosa cells, ovarian growth, and ovulation (2,3). Because the half-life of GnRH secreted in hypothalamus is very short and GnRH is not detected in serum, the action of GnRH in the ovary was thought to be caused by GnRH synthesized within the ovary (4).…”