Newsletter

Table of Contents

24.05.2007

Newsletter No. 3/2007

Anti-MÃ¼llerian hormone and ovarian response.
Moderately elevated FSH and ovarian response.
Pretreatment with estrogens in premature ovarian failure Response to gonadotropin stimulation.
Milder ovarian stimulation â€“ better embryos.

1. Anti-MÃ¼llerian hormone and ovarian response.

Recently, a new marker, the anti-Mullerian hormone (AMH), has been evaluated as a marker of ovarian response. Serum AMH levels have been measured at frequent time-points during the menstrual cycle, suggesting the complete absence of fluctuation. The aim of this study was to evaluate whether serum AMH measurement on any day of the menstrual cycle could predict ovarian response in women undergoing assisted reproductive technology (ART). This study included 48 women attending the IVF/ICSI programme. Blood withdrawal for AMH measurement was performed in all the patients independently of the day of the menstrual cycle. Women in the lowest AMH quartile (<0.4 ng/ml) were older and required a higher dose of recombinant FSH than women in the highest quartile (>7 ng/ml). All the cancelled cycles due to absent response were in the group of the lowest AMH quartile, whereas the cancelled cycles due to risk of ovarian hyperstimulation syndrome (OHSS) were in the group of the highest AMH quartile. This study demonstrated a strong correlation between serum AMH levels and ovarian response to gonadotrophin stimulation. For the first time, clinicians may have a reliable serum marker of ovarian response that can be measured independently of the day of the menstrual cycle.

La Marca A, Guilini S, Tirelli A, Bertucci E, Marsella T, Xella S, Volpe A. Anti-Mullerian hormone measurement on any day of the menstrual cycle strongly predicts ovarian response in assisted reproductive technology.Hum Reprod. 2007

2. Moderately elevated FSH and ovarian response.

To evaluate and compare IVF outcomes of patients within different age categories who had a normal basal FSH level with outcomes of patients with an elevated day 3 FSH level. In a retrospective follow-up study we analyzed 2,708 patients. Of these, 2,477 had normal basal FSH levels, and 231 had elevated basal FSH levels (> or =13.03 IU/L). Patients were segregated into various age groups. Outcomes of IVF overall, including cancellation rates, oocyte yield, and fertilization, implantation, and clinical pregnancy rates (PRs). Cancellation rates were significantly higher in patients with elevated day 3 FSH levels compared with patients with normal FSH levels in all age groups. A significantly lower oocyte yield was observed in patients with elevated basal FSH. Fertilization rates were not affected by FSH levels. A significant decrease in the number of embryos available for transfer in patients > or =38 with an elevated day 3 FSH level was found. Implantation and clinical PRs were lower in patients >40 years of age who had an elevated day 3 FSH level when compared to same age patients with a normal day 3 FSH level. Loss rates were not significantly different. It is concluded that young women with an elevated basal FSH level should be counseled differently than older women, and should be given adequate counseling and granted the opportunity to undergo an IVF cycle.

Luna M, Grunfeld L, Mukherjee T, Sandler B, Copperman AB. Moderately elevated levels of basal follicle-stimulating hormone in young patients predict low ovarian response, but should not be used to disqualify patients from attempting in vitro fertilization. Fertil Steril. 2007 Apr;87(4):782-7.

3. Pretreatment with estrogens in premature ovarian failure Response to gonadotropin stimulation.

The aim of this double-blind, randomized, placebo-controlled study was to evaluate the hypothesis that pretreatment with estrogens in women affected by premature ovarian failure (POF) may improve the results of ovarian stimulation. Fifty women with POF seeking pregnancy were studied. Before starting ovarian stimulation, group 1 received 0.05 mg ethinyl-E(2) (EE) three times a day for 2 weeks, while group 2 received placebo. Ovarian stimulation was carried out with recombinant FSH (r-betaFSH), 200 IU/day/SC. Both EE and placebo were administered during ovarian stimulation. Human chorionic gonadotropin (10,000 IU/IM) was added when the follicle exceeded a mean diameter of 18 mm. Levels of FSH before stimulation were significantly lower in group 1 than in group 2. The rate of ovulation in group 1 (8/25; 32%) was significantly higher than in group 2 (0/25; 0%). Notably, induction of ovulation was successful only in patients whose FSH levels after EE treatment were < or =15 mIU/mL. These data suggest that pretreatment with EE improves the success of rate of ovulation induction with exogenous gonadotropins in patients with POF. A threshold of FSH < or =15 mIU/mL should be achieved before starting ovarian stimulation.

Tartagni M, Cicinelli E, De Perdola G, De Salvia MA, Lavopa G, Loverro G. Effects of pretreatment with estrogens on ovarian stimulation with gonadotropins in women with premature ovarian failure: a randomized, placebo-controlled trial. Fertil Steril. 2007 Apr;87(4):858-61.

4. Milder ovarian stimulation â€“ better embryos.

To test whether ovarian stimulation for in-vitro fertilization (IVF) affects oocyte quality and thus chromosome segregation behaviour during meiosis and early embryo development, preimplantation genetic screening of embryos was employed in a prospective, randomized controlled trial, comparing two ovarian stimulation regimens. Infertile patients under 38 years of age were randomly assigned to undergo a mild stimulation regimen using gonadotrophin-releasing hormone (GnRH) antagonist co-treatment (67 patients), which does not disrupt secondary follicle recruitment, or a conventional high-dose exogenous gonadotrophin regimen and GnRH agonist co-treatment (44 patients). Following IVF, embryos were biopsied at the eight-cell stage and the copy number of 10 chromosomes was analysed in 1 or 2 blastomeres. The study was terminated prematurely, after an unplanned interim analysis (which included 61% of the planned number of patients) found a lower embryo aneuploidy rate following mild stimulation. Compared with conventional stimulation, significantly fewer oocytes and embryos were obtained following mild stimulation (P < 0.01 and < 0.05, respectively). Consequently, both regimens generated on average a similar number (1.8) of chromosomally normal embryos. Differences in rates of mosaic embryos suggest an effect of ovarian stimulation on mitotic segregation errors. Thus, future ovarian stimulation strategies should avoid maximizing oocyte yield, but aim at generating a sufficient number of chromosomally normal embryos by reduced interference with ovarian physiology.

Eijkemans MJ, Van Opstal D, Beckers NG, Verhoeff A, Macklon NS, Fauser BC, Baart EB, Martini E. Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial. Hum Reprod. 2007 Apr;22(4):980-8.

Gerhard Leyendecker