Newsletter

Table of Contents

20.03.2001

Newsletter No.8

Induction of ovulation in infertile women with hyperandrogenism and insulin resistance
Health of 227 children born after controlled ovarian stimulation for in vitro fertilization using the luteinizing releasing hormone antagonist cetrorelix
Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing Controlled ovarian hyperstimulation.
Effects of male age on semen quality and fertility.
Once again: Controlled ovarian hyperstimulation with FSH alone or combined with LH and with what dose

1.Induction of ovulation in infertile women with hyperandrogenism and insulin resistance

Hyperandrogenemia and oligo-amenorrhea are components of PCO-syndrome unless they are caused by an androgen producing tumour or by a defect in adrenal steroid biosynthesis. Though often "typicalâ€ PCO-ovaries might be detected by vaginal ultrasound this finding has not been included as a criterion of PCOS. The prevalence of PCOS in the normal population is about 5% and 30-50% of women with oligo-amenorrhea are suffering from PCO-syndrome. In addition to elevated androgen levels in blood (testosterone, androstenedione, DHEAS) LH levels are sometimes high with an increased LH/FSH ratio. There is probably a multifactorial aetiology to the syndrome. Evidence indicates to increased hypothalamic activity, genetic defects in the adrenal and ovarian steroid biosynthesis and disturbances of the glucose metabolisms as indicated by insulin resistance and hyperinsulinemia. In general, two phenotypes prevail: Lean PCOS. PCOS with adiposity. Elevated LH levels are usually found in lean PCOS women and not in the fat one. That is why an increased LH/FSH ratio is not considered an essential diagnostic criterion for PCOS. Lean women with PCOS usually do not exhibit insulin resistance and hyperinsulinemia. In fat women the probability of insulin resistance is increasing with the weight. A high body-mass-index (BMI), an increased waist to hip ratio and a waist of more than 100 cm are highly predictable for insulin resistance. Insulin resistance is a prognostic sign with respect to the later development of type II diabetes and cardiovascular disease. Moreover, insulin resistance is considered causative in the development of PCOS in obese women. Therefore, lowering of insulin resistance by dietary means, physical activity and drugs is mandatory with respect to the sequel of this derangement but also with respect of restoring ovarian function or improving fertility treatment.

Barbieri RL (2000) Induction of ovulation in infertile women with hyperandrogenism and insulin resistance. Am J. Obstet. Gynecol. 183: 1412-1418

Vandermolen DT, Ratts VS, Evans WS, Stovall DW, Kauma SW, Nestler JE (2001) Metformin increases the ovulatory rate and the pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone. Fertil. Steril. 75: 310-315

2.Health of 227 children born after controlled ovarian stimulation for in vitro fertilization using the luteinizing releasing hormone antagonist cetrorelix

This multicenter study summarises the data from completed phase II and III clinical trial on children born after controlled ovarian stimulation using the luteinizing hormone-releasing hormone antagonist cetrorelix. Two hundred nine and 18 children were born after fresh and frozen embryo transfers, respectively. Of the pregnancies, 76.2% (179 of 234) resulted in live births and ectopic pregnancies occurred in 3.4% (8 of 231); one heterotopic pregnancy and four induced abortions were recorded. The malformation rate among all live births, stillbirths, and aborted fetuses was 3.1%. It is concluded that the use of cetrorelix in controlled ovarian hyperstimulation does not harm subsequently born children.

Ludwig M, RiethmÃ¼ller-Winzen H, Felberbaum RE, Olivennes F, Albano C, Devroey P, Diedrich K (2001) Health of 227 children born after controlled ovarian stimulation for in vitro fertilization using the luteinizing releasing hormone antagonist cetrorelix. Fertil Steril 75: 18-22

3.Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulationy

To assess the efficacy, safety, and local tolerance of ganirelix acetate for the inhibition of premature luteinizing hormone (LH) surges in 313 women undergoing controlled ovarian hyperstimulation (COH) patients were randomised to receive one COH cycle for IVF or ICSI treatment with ganirelix or the reference treatment, a long protocol of leuprolide acetate in conjunction with follitropin-b for injection. The mean number of oocytes retrieved per attempt was 11.6 in the ganirelix group and 14.1 in the leuprolide group. Fertilization rates were 62,4 % and 61,9 % in the ganirelix and leuprolide groups, respectively, and implantation rates were 21,1 % and 26,1 %. Clinical and ongoing pregnancy rates per attempt were 35,4 % and 30,8 % in the ganirelix group and 38,4 % and 36,4 % in the leuprolide acetate group. Fewer moderate and severe injection site reactions were reported with ganirelix (11,9 % and 0,6 %) than with leuprolide (24,4 % and 1,1 %). Ganirelix is effective, safe, and well tolerated. Compared with leuprolide acetate, ganirelix therapy has a shorter duration and fewer injections but produces a similar pregnancy rate.

The North American Ganirelix Study Group (2001) Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation. Fertil Steril. 75: 38-45

4.Effects of male age on semen quality and fertility

English language literature over the last 20 years from January 1, 1980, through December 31, 1999, on the association between male age and semen quality (semen volume, concentration, motility, and morphology) and fertility status (pregnancy rate and time to pregnancy/subfecundity) was reviewed using MEDLINE and Biosis databases. Studies with insufficient numbers of subjects, case reports, case series, or anecdotal data were excluded. Among the methodologically stronger studies, decreases in semen Volume of 3 % - 22 %, decreases in sperm motility of 3 % - 37 %, and decreases in percent normal sperm of 4 % - 18 % were likely when comparing 30-year-old men to 50-year-old men. Most studies examining fertility status suggest a relationship between male age and fertility, but the results are most likely confounded by female partner age. Among studies that did control for male age, comparisons between men under 30 and mend over 50 found relative decreases in pregnancy rates between 23 % and 38 %. A comparison of the various age categories showed that the increased risks for subfecundity ranged from 11 % to 250 %. The weight of the evidence suggests that increased male age ist associated with a decline in semen volume, sperm motility, and sperm morphology but not with sperm concentration.

Kidd AS, Eskenazi B, Wyrobek AJ (2001) Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril 75: 237-248

5.Once again: Controlled ovarian hyperstimulation with FSH alone or in combination with LH and with what dosage?

Recent data indicate that in controlled ovarian hyperstimulation the use of FSH alone is not superior over the use of FSH combined with LH as present in HMG preparations. One of these recent studies was performed to determine the effect of exogenous LH dosage on IVF outcome. Dose and duration of gonadotropin stimulation, follicle and oocyte numbers, implantation rate, and pregnancy rate were studies in four groups of women who received either FSH alone or in combination with LH at a dose of 1, 25 and 75 IU of LH per ampoule. The median duration of ovarian stimulation; median number of gonadotropin ampoules used, serum E2 levels, and numbers of follicles, oocytes, and embryos were similar among the four groups. Median LH levels on the day of hCG administration, however, differed significantly. Live birth rates per cycle differed markedly, but statistical significance was not achieved (23 %, 7 %, 20 %, and 31 % for groups 0, 1, 25, and 75, respectively). A significant trend in implantation rates was noted with increasing LH dosage of the urinary preparations (19 %, 10 %, 18 %, and 28 % for groups 0, 1, 25, and 75, respectively). Although, in this study, the residual endogenous LH after down-regulation was adequate for ovarian response and E2 synthesis, the addition of exogenous LH improved implantation. An FSH/LH ratio of 75/75 IU per ampule appeared to be the optimum dose.

Fillicori M, Cognigni, GE, Taraborrelli S, Spettoli D, Ciampaglia W, Tabarelli de Fatis C, Pocognoli P, Cantelli B, Bosch S (2001) Luteinizing hormone activity in menotropins optimizes folliculogenesis and treatment in controlled ovarian stimulation. J. Clin. Endocrinol. Metab. 86: 337-343

Gordon DU, Harrison AF, Fawzy M, Hennelly B, Gordon AC (2001) A randomized prospective assessor-blind evaluation of luteinizing hormone dosage and in fitro fertilization outcome. Fertil. Steril. 75: 324-331

Strehler E, Abt M, El-Danasouri I, De Santo M, Sterzik K (2001) Impact of recombinant follicle-stimulating hormone and human menopausal gonadotropins on in vitro fertilization outcome. Fertil. Steril. 75: 332-341

Ng EHY, Lau EYL, Yeung WSB, Ho PC (2001) HMG is as good as recombinant human FSH in terms of oocyte and embryo quality: a prospective and randomized trial. Hum. Reprod. 16: 319-325

Gerhard Leyendecker