J. Salat-Baroux

Clinical Assessment of Recombinant Human Follicle-Stimulating Hormone in Stimulating Ovarian Follicular Development Before In Vitro Fertilization

OBJECTIVE To compare the efficacy and the safety of recombinant human FSH (hFSH) with urinary hFSH for stimulating follicular development in women undergoing IVF-ET. DESIGN Multicenter, prospective, randomized, open, parallel group, clinical study. SETTING Eight European academic IVF units and one private IVF unit. PATIENTS Infertile female patients aged 18 to 38 years suffering from tubal disease, mild endometriosis, or unexplained infertility. INTERVENTIONS Pretreatment with buserelin acetate was followed by recombinant or urinary hFSH treatment started at an initial dose of 225 IU FSH/d. Dose adjustment was allowed after 5 days of FSH. After administration of hCG, a standard IVF-ET procedure was performed. MAIN OUTCOME MEASURES Follicular development, oocyte retrieval, fertilized oocytes, duration and dose of FSH, and pregnancy. The hypothesis formulated before the study was that no difference was expected between the two FSH preparations. RESULTS Sixty patients were treated with recombinant hFSH and 63 with urinary hFSH. The mean number (+/- SD) of growing follicles (mean diameter > 10 mm) was 10.3 +/- 4.9 and 11.2 +/- 5.2, of follicles (mean diameter > 14 mm) was 7.8 +/- 3.6 and 9.2 +/- 4.5, of retrieved oocytes was 9.3 +/- 5.0 and 10.7 +/- 5.3, and of fertilized oocytes was 5.6 +/- 3.8 and 6.5 +/- 4.3, for recombinant and urinary hFSH, respectively. The duration of FSH treatment was 9.9 +/- 2.3 and 9.4 +/- 1.8 days and the average total dose was 2270 +/- 714 and 2095 +/- 591 IU of FSH, for recombinant and urinary hFSH, respectively. Thirteen pregnancies were recorded in the recombinant hFSH group and 11 in the urinary hFSH group. Nine patients delivered 13 live infants in the recombinant hFSH group and eight delivered 13 live infants in the urinary hFSH group. In terms of safety, no difference was recorded between the groups and no anti-FSH antibodies were found in any of the patients. CONCLUSIONS This clinical study shows that recombinant hFSH is as safe and effective as urinary hFSH in stimulating ovarian follicular development.

Ultrastructure of the human preovulatory oocyte

The ultrastructure of preovulatory human oocyte—cumulus complexes was described after inducing maturation by clomiphene, human menopousal gonadotropin (hMG), human chorionic gonadotropin (hCG) treatment. The majority of the oocytes was at metaphase, II of meiosis, with a radially orientated spindle. The oocyte surface was covered by a multitude of microvilli. Cortical granules were nonuniformly distributed along the cortex. A cytoplasmic polarization was observed. The cytoplasmic organelles were in general uniformly dispersed, with the exception of a narrow segment within which cytoplasmic membranes and mitochondria formed clusters. The spirndle was usually found at the borderline between the two regions of the cytoplasm. The functional significance of this polarization is not yet known.

Diagnosis and treatment of intrauterine adhesions by microhysteroscopy

In this report of 69 patients, a new type of hysteroscope was used to evaluate the extent and character of intrauterine adhesions, to perform lysis of them, and to monitor the effects of therapy. Additionally, prospective studies with regard to pathogenesis and endometrial regeneration can be achieved in vivo. In 59 patients the procedures were performed in an office setting using a CO2 hysteroscopic technique without the need for local anesthesia or cervical dilatation. Of 30 infertile patients, 38% subsequently had uncomplicated deliveries. The severe forms of this disease still remain very difficult to treat effectively. When the adhesions were severe or the procedure painful, the operation was scheduled under general anesthesia (ten cases). A sequential hysteroscopy with good patient acceptance affords additional opportunity for removing residual adhesions and intrauterine devices, and serves as a basis for ending treatment with steroids.

A multiparametric analysis of endometrial estrogen and progesterone receptors after the postovulatory administration of mifepristone.

A double-blind randomized study was performed in two groups of eight normally cycling patients: group I received 10 mg/d of RU486 for 4 days from the date of ovulation and group II received a placebo. On day +5, cytosol and endometrial estrogen receptors (ERs), and progesterone receptors (PRs) were analyzed by radioligand binding assay as well as by enzyme immunochemistry. Histologic studies showed that all the endometria of group I were abnormal (luteal insufficiency and/or E/P imbalance). The nuclear PR levels were significantly higher in group I (843 +/- 422 fmol/mg) deoxyribonucleic (DNA) compared with 482 +/- 232 fmol/mg DNA in group II. Immunohistochemical study showed that ER and PR staining was higher for both glands and stroma in group I (52% and 72% for the respective receptors), compared with the receptor-immunostained surface observed in group II, which was reduced to 40% for ER and to 4% for PR. This study demonstrates that RU486 administered in the immediate postovulatory period blocks normal tissue evolution in the follicular phase as well as the processing of PR.

Lone hyperuricemia during pregnancy: Maternal and fetal outcomes

OBJECTIVE Study of maternal and fetal consequences of lone hyperuricemia during pregnancy and demonstration that lone hyperuricemia is not a risk factor regarding the onset of preeclampsia. STUDY DESIGN Retrospective study of two groups of women, one found to have lone hyperuricemia during pregnancy (n=102) and the others with normal serum uric acid levels (n=100). RESULTS The only consequence identified of the lone hyperuricemia was a lower birth weight of children born to mothers found to have lone hyperuricemia for more than 2 weeks (P<0.05). CONCLUSIONS Lone hyperuricemia is not a risk factor regarding the onset of preeclampsia. It is therefore unnecessary to measure serum uric acid level during a normal pregnancy.

Morphologic and Cytologic Study of Human Embryos Obtained by In Vitro Fertilization

Among the main reasons for implantation failure of human embryos obtained by IVF, the embryo viability is the most difficult parameter to analyse. Indeed, as embryos are replaced at the two- or four-cell stage, nothing is known about their developmental capacity. For this purpose, we investigated the morphologic and cytologic aspects of the embryos obtained during the last year.

Roxithromycin treatment of mouse chlamydial salpingitis and protective effect on fertility.

We used a mouse model of acute chlamydial salpingitis to evaluate the efficacy of roxithromycin in preventing irreversible inflammatory damage leading to tubal infertility. Female C3H/He mice were genitally inoculated with a human strain of Chlamydia trachomatis and then treated with roxithromycin glutamate subcutaneously. Treatment was initiated either 7 or 10 days postinfection (p.i.) and continued for 7 days at a dosage of 50 or 100 mg/kg of body weight per 24 h. The course of the disease was monitored serologically, bacteriologically, and histologically. At the end of the treatment, the mice were encaged with males and their reproductive capacity was recorded over a 19-week period. The protective effect of roxithromycin was assessed in terms of fertility parameters in comparison with values for noninfected control mice. When treatment was initiated on day 7 p.i. and given in twice-daily 25-mg/kg doses, all the mice remained fertile and the total number of offspring was similar to that of sham-infected mice (17.3 +/- 3.3 versus 17.2 +/- 2.3). When treatment was initiated on day 10 p.i. and given in a single daily dose of 50 or 100 mg/kg, 90 and 70% of the mice, respectively, remained fertile; however, in terms of total offspring, fertility was lower in the group treated with the lower dose (5.6 +/- 1.4 versus 13.0 +/- 3.8). Roxithromycin was found to be effective against C. trachomatis in the mouse genital tract, but fertility was only partially preserved when the time between infection and treatment was prolonged. Images

Multiple pregnancies: the price to pay

Since 1980, the rate of multiple pregnancies due to assisted reproductive technology has been multiplied by 10, especially for twin pregnancies and for cases involving simple stimulation of ovulation. The prices paid are: an increase in prematurity (82% of deliveries); perinatal mortality (an increase of 74%); and transfer to intensive care units (95% of infants born of multiple pregnancies). This does not take into account the rise in cost per child, which increased by 1.9 for twins and 3.7 for triplets. The solution does not lie in selective embryo reduction but in the reduction of the number of embryos transferred.

Hormonal secretions in singleton pregnancies arising from the implantation of fresh or frozen embryos after oocyte donation in women with ovarian failure

Objective To determine whether levels of human chorionic gonadotropin (hCG), 17 β -estradiol (E 2 ), and progesterone (P) are different in the peri-implantation phase of fresh versus frozen embryos. Design Hormonal secretions were measured on days 9 and 11 after implantation and at 4, 5, and 6 weeks gestation. Patients Thirty-one pregnancies were achieved in 65 patients with ovarian failure. Seventeen singleton pregnancies developed after implantation of 4 frozen and 13 fresh embryos. Results Human chorionic gonadotropin and E 2 , contrary to P, were higher in cases of fresh embryos from the 9th day after transfer to the 5th week at which time they become statistically significant (respectively, for hCG and E 2 , 5,800.3 ± 332.3 versus 2,027.3 ± 916.3 [mean ± SD] mIU/mL for hCG and 562.3 ± 215 versus 291 ± 152 pg/mL for E 2 ). Conclusions This difference might be explained by either the higher number of fresh embryo replaced or by the fact that the number of blastomeres and also their metabolic activity could be reduced after freezing and thawing.

Programmed ovulation induction and oocyte retrieval for in vitro fertilization

Forty-two patients underwent programmed ovulation induction for oocyte retrieval. They were treated in the preceding cycles with a progestagen, ethynodiol diacetate, at a dose of 2 mg twice daily. Two groups were defined based upon the stimulation protocol: Group A1 was stimulated with clomiphene citrate and human menopausal gonadotropin (hMG), and Group A2 with follicle-stimulating hormone (FSH) and hMG. They were compared to two randomized control groups of patients who received the same induction but were classically monitored. There was a high proportion of spontaneous ovulations in the programmed group (8/42) compared to the nonprogrammed group (0/42). There was a nonsignificant difference in the number of oocytes obtained or embryos replaced per cycle. Four pregnancies were obtained in the programmed group (24% per transfer), against 10 in the nonprogrammed patients (32% per transfer). The results of this method seem to be better using FSH for ovulation stimulation and a verification of the serum estradiol on the day of induction with human chorionic gonadotropin (hCG) and the following day (semiprogrammed method).