Newsletter

Table of Contents

26.09.2006

Newsletter No. 5/2006

Reproductive Medicine

Ovulation induction with clomiphene citrate plus dexamethazone.
Recurrence rate of endometriosis after ovarian hyperstimulation
Endometriosis and the appendix
In vitro fertilization with single blastocyst-stage transfer

1. Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebo-controlled study.

The aim of this work was to evaluate the efficacy of adding dexamethazone (DEX) (high dose, short course) to clomiphene citrate (CC) in CC-resistant polycystic ovary syndrome (PCOS) with normal dehydroepiandrosterone sulphate (DHEAS) in induction of ovulation. Eighty infertile women with CC-resistant PCOS were randomly assigned into two groups. Group I: Clomiphene citrate 100 mg/day was given from day 3 to day 7 of the cycle and DEX 2 mg/day from day 3 to day 12 of the cycle. Group II: Same protocol of CC combined with placebo (folic acid tablets) was given from day 3 to day 12 of the cycle. The main outcome was ovulation. Secondary measures included number of follicles >18 mm endometrial thickness and pregnancy rate. Ovarian follicular response was monitored by transvaginal ultrasound. HCG 10,000 U was given when at least one follicle measured 18 mm, and timed intercourse was advised. There were no statistically significant differences between groups as regards age, duration of infertility, BMI, waist-hip ratio (WHR), menstrual pattern, hirsutism, serum DHEAS or day of HCG administration. The mean number of follicles>18 mm at the time of HCG administration and the mean endometrial thickness were significantly higher in the DEX group than in the placebo group (P<0.05). Similarly, there were significantly higher rates of ovulation (75 versus 15%) (P<0.001) and pregnancy (40 versus 5%) (P<0.05) in the DEX group. Dexamethazone was very well tolerated as no patients complained of any side effect. There was a significant difference between the responders and non-responders in the presence of oligomenorrhea, amenorrhea or hirsutism. It is concluded that induction of ovulation by adding DEX (high dose, short course) to CC in CC-resistant PCOS with normal DHEAS is associated with no adverse anti-estrogenic effect on the endometrium and higher ovulation and pregnancy rates in a significant number of patients. Induction with DEX appears to be independent on age, period of infertility, BMI or WHR.

Elnashar A, Abdelmageed E, Fayed M, Sharaf M. Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebo-controlled study. Hum Reprod. 2006 Jul;21(7):1805-8. Epub 2006 Mar 16.

2. Is the endometriosis recurrence rate increased after ovarian hyperstimulation?

To test the hypothesis that the cumulative endometriosis recurrence rate (CERR) after fertility surgery for endometriosis stage III or IV is increased in women exposed to very high E(2) levels during ovarian hyperstimulation (OH) for IVF when compared with women exposed to less high E(2) levels during OH for intrauterine insemination (IUI) a retrospective cohort study including infertility patients with endometriosis stage III or IV between 1990 and 2001 was performed. Patients (n = 67) with endometriosis stage III (n = 45) or IV (n = 22) who underwent pelvic reconstructive surgery and subsequently started fertility treatment with either IVF only (n = 39), both IVF and IUI in different cycles (n = 11), or IUI only (n = 17) were investigated. Life table analysis was used to calculate the CERR based on histologic or cytologic proof of disease recurrence. At 21 months after the start of OH the overall CERR was 31% and was significantly lower in patients treated with IVF only (7%) or women treated with both IVF and IUI in different cycles (43 %) than in those treated with IUI only (70%). At 36 months after the start of OH, the overall CERR was 63%. In contrast to our hypothesis, the results from this study showed that the CERR is lower after ovarian hyperstimulation for IVF than after lower-dose ovarian stimulation for IUI, suggesting that temporary exposure to very high E(2) levels in women during OH for IVF is not a major risk factor for endometriosis recurrence in women treated with assisted reproductive technology.

D'Hooghe TM, Denys B, Spiessens C, Meuleman C, Debrock S Is the endometriosis recurrence rate increased after ovarian hyperstimulation? Fertil Steril. 2006 Aug;86(2):283-90. Epub 2006 June 6

3. Endometriosis and the appendix: a case series and comprehensive review of the literature.

The study was undertaken to report the prevalence of appendiceal disease in women with chronic pelvic pain undergoing laparoscopy for possible endometriosis, summarize the literature, and more accurately estimate the prevalence of endometriosis of the appendix. One hundred thirty-three patients with chronic pelvic pain and possible endometriosis undergoing laparoscopy were studied. Of 133 patients, 13 had a previous appendectomy with unknown pathology. Of the remaining 120 patients, 109 reported right lower quadrant pain. Of this subgroup, six patients had appendiceal pathology: four with pathology-confirmed endometriosis, one with Crohn's disease suspected at laparoscopy, and one with chronic appendicitis. The prevalence of appendiceal endometriosis in patients with biopsy-proven endometriosis (n = 97) or with right lower quadrant pain (n = 109) was 4.1% and 3.7%, respectively. This rate was similar to the 2.8% prevalence confirmed by literature review in patients with endometriosis but was much higher than that reported in all patients (0.4%). Appendiceal endometriosis, while relatively uncommon in patients with endometriosis, is rare in the general population. In patients with right lower quadrant or pelvic pain, the appendix should be inspected for endometriosis and evidence of nongynecologic disease.

Gustofson RL, Kim N, Liu S, Stratton P. Endometriosis and the appendix: a case series and comprehensive review of the literature.Fertil Steril. 2006 Aug;86(2):298-303. Epub 2006 Jul 7

4. In vitro fertilization with single blastocyst-stage transfer

Single-embryo transfer has been recommended to reduce the incidence of multiple gestations when in vitro fertilization is performed in women under 36 years of age. A prospective, randomized, controlled trial was designed to determine whether there were any differences in the rates of pregnancy and delivery between women undergoing transfer of a single cleavage-stage (day 3) embryo and those undergoing transfer of a single blastocyst-stage (day 5) embryo. Infertile women under 36 years of age (n=351) were studied who were randomly assigned to undergo transfer of either a single cleavage-stage embryo (176 patients) or a single blastocyst-stage embryo (175 patients). Multifollicular ovarian stimulation was performed with a gonadotropin-releasing hormone antagonist and recombinant follicle-stimulating hormone. The study was terminated early after a prespecified interim analysis (which included 50 percent of the planned number of patients) found a higher rate of pregnancy among women undergoing transfer of a single blastocyst-stage embryo (P=0.02). The rate of delivery was also significantly higher in this group than in the group undergoing transfer of a single cleavage-stage embryo (32.0 percent vs. 21.6 percent; relative risk, 1.48; 95 percent confidence interval, 1.04 to 2.11). Two multiple births occurred, both of monozygotic twins, both of which were in the group undergoing transfer of a single cleavage-stage embryo. These findings support the transfer of a single blastocyst-stage (day 5) embryo in infertile women under 36 years of age. Copyright 2006 Massachusetts Medical Society.

Papanikolaou EG, Camus M, Kolibianakis EM, Van Landuyt L, Van Steirteghem A, Devroey P. In vitro fertilization with single blastocyst-stage versus single cleavage-stage embryos. N Engl J Med. 2006 Mar 16;354(11):1139-46.

Gerhard Leyendecker