Newsletter

Table of Contents

20.03.2003

Newsletter Nr. 20

Treatment of hyperandrogenic alopecia in women.
Developmental outcome at 2 years of age for children born after ICSI compared with children born after IVF.
Chromosomal abnormalities and embryo development in recurrent miscarriage couples
Urinary incontinence after vaginal delivery or cesarean section

1.Treatment of hyperandrogenic alopecia in women

The study was undertaken to determine the effectiveness of various antiandrogens for the treatment of premenopausal women with hyperandrogenic alopecia. Forty-eight hyperandrogenic women were studied (mean age 25 Â± 2 years, mean body mass index [BMI] 24.3 Â± 2) who presented consecutively with the chief complaint and diagnosis of androgenic alopecia over a period of 3 years. Only premenopausal women with increased serum androgens were included. Serum androgens that were higher than the mean Â± 2 SD of levels in ovulatory controls were considered elevated. Frontal hair thinning was assessed as grade I, II, or III according to the Ludwig classification. A picture of the frontalâ€“parietal region was obtained in each patient and was used for comparisons at the end of the treatment. Mild hirsutism (evaluated by Ferriman-Gallwey-Lorenzo index) was present in 10 patients (21%) and menstrual irregularities (oligomenorrhea) were present in 20 women (42%) with androgenetic alopecia. Thirty normal ovulatory women, matched for age and body weight, served as controls. In all patients and controls, a blood sample was obtained during the follicular phase of the cycle (days 5â€“6), after an overnight fast for T, unbound T, and DHEAS. These values were used to confirm the presence of hyperandrogenism in all 48 subjects with androgenic alopecia.
Thirty-six women were randomized to one of three treatments, each composed of 12 subjects: 1. cyproterone acetate (CPA) (50 mg/day + 25 g of ethinyl estradiol [EE]) in a reverse sequential regimen (CPA from day 5 to day 15 of the cycle + EE from day 5 to day 25 of the cycle); 2. flutamide (250 mg/day); and 3. finasteride (5 mg/day). A dose of 250 mg was chosen for flutamide to minimize the potential for hepatic toxicity. Twelve women who were recruited for the study refused any treatment and were observed for 1 year without any therapy. These women had similar characteristics and the same degree of alopecia as women in the treatment groups. The main outcome measures were Ludwig scores for hair thinning as well as patient and investigator assessments of treatment effectiveness. Flutamide resulted in a reduction of 21% in Ludwig scores (2.3 +/- 0.2 to 1.8 +/- 0.1). The other treatment effects were not statistically significant. Patient and investigator assessments showed a similar trend. It is concluded that Flutamide at a dose of 250 mg daily induced a modest improvement in alopecia after 1 year, whereas cyproterone acetate and finasteride were not effective. Treatment for more than 1 year may be required for better results.

Carmina E, Lobo RA. Treatment of hyperandrogenic alopecia in women. Fertil Steril. 2003 79, 91-95.

Ludwig E. Classification of the types of androgenic alopecia (common baldness occurring in the female sex) Br J Dermatol 1977, 97:247-254

2. Developmental outcome at 2 years of age for children born after ICSI compared withchildren born after IVF.

Since the introduction of ICSI in 1991, medical outcome studies on ICSI children have been performed, but few have addressed developmental outcome. Hence, this outcome was assessed by performing a standard developmental test on children born after ICSI as compared with children born after IVF, at the age of 2 years. In a prospective study, the medical and developmental outcome of 439 children born after ICSI (378 singletons, 61 twins) were compared with those of 207 children born after IVF (138 singletons, 69 twins), at the age of 24-28 months. These children were part of a cohort of children followed since birth. Of children reaching the age of 24-28 months between May 1995 and March 2002, 44.3% (2375/5356) were examined by a paediatrician who was unaware of the type of treatment used for each couple. Of all the children born, 12.2% (439/3618) in the ICSI group and 11.9% (207/1738) in the IVF group underwent a formal developmental assessment using the Bayley Scale of Infant Development (mental scale) by a paediatrician blinded to the type of treatment
There was no significant difference in maternal educational level, maternal age, gestational age, parity, birthweight, neonatal complication rate or malformation rate at 2 years between ICSI and IVF singletons, or between ICSI and IVF twins. No significant difference was observed in the developmental outcome using the Bayley scale at the age of 24-28 months (raw scores or test age) between ICSI children or IVF children. A multivariate regression analysis for the singleton children indicated that parity, sex (boys had lower scores than girls) and age had a significant influence on the test result, but that the fertility procedure (ICSI versus IVF) did not influence the test result. ICSI children from fathers with low sperm concentration, low sperm motility or poor morphology had a similar developmental outcome to that of children from fathers with normal sperm parameters. There were no significant differences between the initial cohort and the group lost to follow-up, nor between the psychologically tested and the non-tested group for a number of variables such as maternal educational level, birthweight in singletons and neonatal malformation rate. Although only some of the cohort of ICSI children were evaluated, a representative sample of both ICSI and IVF children was compared. In conclusion, there is no indication that ICSI children have a lower psychomotor development than IVF children. Paternal risk factors associated with male-factor infertility were found not to play a role in developmental outcome.

Bonduelle M, Ponjaert I, Steirteghem AV, Derde MP, Devroey P, Liebaers I. Developmental outcome at 2 years of age for children born after ICSI compared with children born after IVF. Hum Reprod. 2003 Feb;18(2):342-50.

3. Chromosomal abnormalities and embryo development in recurrent miscarriage couples.

Chromosomal abnormalities are an important cause of spontaneous abortion and recurrent miscarriage (RM). Therefore, the authors have analysed the incidence of chromosomal abnormalities and embryo development in patients with RM. Preimplantation genetic diagnosis (PGD) was performed on 71 couples with RM and 28 couples undergoing PGD for sex-linked diseases (control group). Chromosomes 13, 16, 18, 21, 22, X and Y were analysed by fluorescence in-situ hybridization. The implantation rate in RM patients was 28% and three patients (13%) miscarried. The percentage of abnormal embryos was significantly increased (P < 0.0001) in RM patients compared with controls (70.7 versus 45.1%). All of the embryos were abnormal in 19 cycles (22.1%) and repeated PGD cycles yielded similar rates of chromosomal abnormalities in 14 couples. Anomalies for chromosomes 16 and 22 were significantly higher (P < 0.01) in RM cases. In the RM population, euploid embryos reached the blastocyst stage more frequently than abnormal embryos (61.7 versus 24.9%; P < 0.0001). Thus, RM is associated with a higher incidence of chromosomally abnormal embryos, of which some are able to develop to the blastocyst stage. IVF plus PGD is an important step in the management of these couples, but the technique has to move towards a full chromosome analysis.

Rubio C, Simon C, Vidal F, Rodrigo L, Pehlivan T, Remohi J, Pellicer A. Chromosomal abnormalities and embryo development in recurrent miscarriage couples. Hum Reprod. 2003 Jan;18(1):182-8.

4. Urinary incontinence after vaginal delivery or cesarean section.

It is uncertain whether women who deliver by cesarean section have an increased risk of urinary incontinence as compared with nulliparous women and whether women who deliver vaginally have an even higher risk. The investigators studied 15,307 women enrolled in the Epidemiology of Incontinence in the County of Nord-Trondelag (EPINCONT) study, which involved a community-based cohort. The data base for this study was linked to data from the Medical Birth Registry of Norway. Included were women who answered questions related to urinary incontinence, were younger than 65 years of age, and had had no deliveries, cesarean sections only, or vaginal deliveries only. The prevalence of any incontinence was 10.1 percent in the nulliparous group; age-standardized prevalences were 15.9 percent in the cesarean-section group and 21.0 percent in the vaginal-delivery group. Corresponding figures for moderate or severe incontinence were 3.7 percent, 6.2 percent, and 8.7 percent, respectively; figures for stress incontinence were 4.7 percent, 6.9 percent, and 12.2 percent, respectively; figures for urge incontinence were 1.6 percent, 2.2 percent, and 1.8 percent, respectively; and figures for mixed-type incontinence were 3.1 percent, 5.3 percent, and 6.1 percent, respectively. As compared with nulliparous women, women who had cesarean sections had an adjusted odds ratio for any incontinence of 1.5 (95 percent confidence interval, 1.2 to 1.9) and an adjusted odds ratio for moderate or severe incontinence of 1.4 (95 percent confidence interval, 1.0 to 2.1). Only stress and mixed-type incontinence were significantly associated with cesarean sections. The adjusted odds ratio for any incontinence associated with vaginal deliveries as compared with cesarean sections was 1.7 (95 percent confidence interval, 1.3 to 2.1), and the adjusted odds ratio for moderate or severe incontinence was 2.2 (95 percent confidence interval, 1.5 to 3.1). Only stress incontinence (adjusted odds ratio, 2.4; 95 percent confidence interval, 1.7 to 3.2) was associated with the mode of delivery. It is concluded from these data that the risk of urinary incontinence is higher among women who have had cesarean sections than among nulliparous women and is even higher among women who have had vaginal deliveries. However, these findings should not be used to justify an increase in the use of cesarean sections.

Rortveit G, Daltveit AK, Hannestad YS, Hunskaar S Norwegian Epidemiology of Incontinence in the County of Nord-Trondelag Study. Urinary incontinence after vaginal delivery or cesarean section. N Engl J Med. 2003 Mar 6;348(10):900-7.

Gerhard Leyendecker