Luteal phase start of low-dose FSH priming of follicles results in an efficient recovery, maturation and fertilization of immature human oocytes

Abstract

In this prospective study we investigated whether the maturation and fertilization of immature oocytes can be improved by administration of recombinant follicle stimulating hormone (rFSH) starting in the late luteal phase in two groups of women: group 1 (n = 6) women with regular menstrual cycles; and group 2 (n = 6) women with irregular cycles and polycystic ovaries (PCO) on ultrasound examination. Low-dose (37.5 IU) rFSH was commenced 11 days after LH surge during a spontaneous menstrual cycle and on the ninth day of progesterone administration in an irregular cycle. Recombinant FSH was continued until the leading follicle was approximately 10 mm in diameter. The oocytes were retrieved after withdrawing rFSH for 2-5 days. In total, 136 oocytes were recovered (group 1, 67 oocytes; group 2, 69 oocytes). Nine of the oocytes from PCO women were atretic at retrieval. Oocytes complete with cumulus cells were cultured for 44 h in complex tissue culture medium supplemented with gonadotrophins and fetal calf serum. After maturation, the cumulus cells were removed and metaphase II oocytes were injected with spermatozoa. Respectively, the oocyte maturation and fertilization rates were 64 and 72% in group 1, and 78 and 57% in group 2 (not significant). After fertilization, the zygotes (group 1, n = 22; group 2, n = 11) and cleavage stage embryos (group 1, n = 9; group 2, n = 15) were frozen in propanediol. All women except one (11/12) had approximately five zygotes or cleaved embryos frozen. The viability of in-vitro matured frozen-thawed embryos was generally poorer than that (81%) seen after conventional intracytoplasmic sperm injection, with 61% survival in group 1 and 23% in group 2. Fifteen embryo transfers resulted in one miscarriage at 6 weeks gestation. The late luteal start of low-dose rFSH yielded a good number of immature oocytes in women with both regular and irregular cycles. Two out of three of these oocytes matured and fertilized. However, cryosurvival of the zygotes and cleaved embryos was unsatisfactory and thus cryopreservation of in-vitro matured embryos may not be an optimal procedure.

Ovarian stimulation in the luteal phase: systematic review and meta-analysis

“…Human chorionic gonadotropin (hCG) was the predominant medication used to induce oocyte maturation. Although four authors induced maturation with a GnRH agonist [10,[27][28][29], three authors used either hCG or GnRH agonist depending on the clinical scenario [11,30,31], and one author performed in vitro maturation following neither hCG nor a GnRH agonist [32]. All of the included studies reported the primary outcome of number of oocytes retrieved.…”

“…Eight of the qualitative studies were excluded due to the lack of a control group or due to a sample size of only one subject [8,10,28,32,[35][36][37][38].…”

Human oocyte maturation in vitro

“…Granulosa cells of antral follicles are responsive to FSH and it is conceivable that administration of even small doses of this hormone may improve the follicle health status and increase the number and quality of retrieved oocyte. Between 1999 and 2000, this approach was initially tested in normovulatory and PCO women with results not always consistent (Suikkari et al, 2000;Mikkelsen and Lindenberg, 2001). A more recent study does not seem to demonstrate a clear advantage in the delivery of FSH to normovulatory women .…”

In vitro maturation may prevent the cancellation of in vitro fertilization cycles in poor responder patients: A case report

“…Accordingly, Lin et al (10) could not find any beneficial effect of FSH priming on the number of oocytes retrieved, maturation and fertilization rates. Conversely, Suikkari et al (11) reported that a small dose of FSH in women undergoing regular menstruation might increase the yield of immature oocytes collected. Junk et al (12) also demonstrated in their study in 2003 that FSH priming improves oocyte maturation, but does not have an effect on subsequent embryonic development.…”