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This randomized, single-blind, multicentre, multinational study compared recombinant human FSH (rhFSH, Gonal-F) with highly purified urinary human FSH (uhFSH, Metrodin HP) in women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI). Following desensitization in a long gonadotrophin-releasing hormone (GnRH) agonist protocol, patients received s.c. Gonal-F or Metrodin HP, at a fixed dose of 150 IU, until there was adequate follicular development. Of 496 women randomized, 232 and 231 in the Gonal-F and Metrodin HP groups respectively received human chorionic gonadotrophin (HCG). The duration of FSH treatment was significantly shorter with Gonal-F than with Metrodin HP (11.6 +/- 1.9 days versus 12. 4 +/- 2.7 days; P < 0.0001) and significantly fewer ampoules were required (mean 22.6 +/- 5.0 versus 24.3 +/- 5.1, P < 0.0002). There were, however, significantly more follicles > or =10 mm in diameter with Gonal-F (15.6 +/- 8.2 versus 13.6 +/- 7.1, P < 0.01) and oocytes retrieved (13.1 +/- 7.7 versus 11.4 +/- 7.6, P < 0.002). Although no statistical difference in pregnancy rate was recorded, patients receiving Gonal-F had a higher pregnancy rate per cycle than patients given Metrodin HP (25.1 versus 20.1%). Moderate to severe ovarian hyperstimulation syndrome occurred in 2.8 and 1.2% of Gonal-F and Metrodin HP patients respectively (not significant). In conclusion, FSH stimulation in combination with a long GnRH agonist protocol is effective in inducing multiple follicular development and embryos with a high implantation potential. However, Gonal-F is clearly more effective than Metrodin HP in inducing multifollicular development.

This randomized, single-blind, multicentre, multinational study compared recombinant human FSH (rhFSH, Gonal-F®) with highly purified urinary human FSH (uhFSH, Metrodin HP®) in women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI). Following desensitization in a long gonadotrophin-releasing hormone (GnRH) agonist protocol, patients received s.c. Gonal-F® or Metrodin HP®, at a fixed dose of 150 IU, until there was adequate follicular development. Of 496 women randomized, 232 and 231 in the Gonal-F® and Metrodin HP® groups respectively received human chorionic gonadotrophin (HCG). The duration of FSH treatment was significantly shorter with Gonal-F® than with Metrodin HP® (11.6 ± 1.9 days versus 12.4 ± 2.7 days; P < 0.0001) and significantly fewer ampoules were required (mean 22.6 ± 5.0 versus 24.3 ± 5.1, P < 0.0002). There were, however, significantly more follicles ≥10 mm in diameter with Gonal-F® (15.6 ± 8.2 versus 13.6 ± 7.1, P < 0.01) and oocytes retrieved (13.1 ± 7.7 versus 11.4 ± 7.6, P < 0.002). Although no statistical difference in pregnancy rate was recorded, patients receiving Gonal-F® had a higher pregnancy rate per cycle than patients given Metrodin HP® (25.1 versus 20.1%). Moderate to severe ovarian hyperstimulation syndrome occurred in 2.8 and 1.2% of Gonal-F® and Metrodin HP® patients respectively (not significant). In conclusion, FSH stimulation in combination with a long GnRH agonist protocol is effective in inducing multiple follicular development and embryos with a high implantation potential. However, Gonal-F® is clearly more effective than Metrodin HP® in inducing multifollicular development.

This prospective study examines the benefits of using natural cycles instead of stimulated cycles in poor responders to in-vitro fertilization (IVF) treatment. Eleven patients in whom puncture was cancelled or who failed to conceive because of a poor response were included in the analysis. The data for natural cycles (n = 16) were compared with data obtained during previous stimulated cycles (n = 25) in the same women. Out of 16 natural cycles, 13 (81.3%) were scheduled for oocyte retrieval compared to 13 out of 25 stimulated cycles (52%). Eighteen metaphase II oocytes were obtained during stimulated cycles, giving a 66% fertilization rate. In natural cycles, 11 metaphase II oocytes were available giving a fertilization rate of 78.6%. A mean number of 51.5 ± 25 ampoules of gonadotrophins per cycle were used during ovarian stimulation. Three clinical pregnancies were obtained after embryo transfer in natural cycles (18.8%/started cycle) compared to none in stimulated cycles. Our findings demonstrate that an encouraging number of pregnancies can be achieved by IVF during natural cycles in poor responders to ovarian stimulation. This may not be the first approach to consider in IVF but it should be offered as an alternative after two ovarian response failures using classical protocols of stimulation.

This prospective study examines the benefits of using natural cycles instead of stimulated cycles in poor responders to in-vitro fertilization (IVF) treatment. Eleven patients in whom puncture was cancelled or who failed to conceive because of a poor response were included in the analysis. The data for natural cycles (n = 16) were compared with data obtained during previous stimulated cycles (n = 25) in the same women. Out of 16 natural cycles, 13 (81.3%) were scheduled for oocyte retrieval compared to 13 out of 25 stimulated cycles (52%). Eighteen metaphase II oocytes were obtained during stimulated cycles, giving a 66% fertilization rate. In natural cycles, 11 metaphase II oocytes were available giving a fertilization rate of 78.6%. A mean number of 51.5 +/- 25 ampoules of gonadotrophins per cycle were used during ovarian stimulation. Three clinical pregnancies were obtained after embryo transfer in natural cycles (18.8%/started cycle) compared to none in stimulated cycles. Our findings demonstrate that an encouraging number of pregnancies can be achieved by IVF during natural cycles in poor responders to ovarian stimulation. This may not be the first approach to consider in IVF but it should be offered as an alternative after two ovarian response failures using classical protocols of stimulation.

Micromanipulation of mouse gametes with a commercially available compact laser microbeam system was studied. Both the normal in-vitro fertilization (IVF) group and the laser zona dissection (LZD) group were tested under normal (2 x 10(6) motile spermatozoa/ml) and low (500,000 motile spermatozoa/ml) insemination conditions. Subzonal insemination (SUZI) was also tried in a small group of gametes and the results were compared with those of the low insemination groups. Fertilization rates and blastocyst formation rates for the IVF and the LZD-treated groups were respectively 53 and 60% and 60 and 78%, which were not significantly different. However, under low insemination conditions, the results were significantly better in the LZD-treated group (58% fertilization rate and 83% blastocyst formation rate) compared to the results of the IVF group (33 and 48%) (P < 0.05). The SUZI-treated group showed the lowest fertilization rate (18%). No significant difference between the LZD and the IVF group was observed with respect to parthenogenetic activation. LZD has a beneficial effect on fertilization rates in cases of reduced sperm quality.

The management of large endometriomas was described in a series of 814 patients. Combined therapy using gonadotrophin-releasing hormone agonist (GnRHa) and carbon dioxide laser laparoscopy was proposed. Drainage and GnRHa for 12 weeks provoked a reduction of the endometrioma size up to 50% of the initial value. After vaporization of the internal wall, a cumulative pregnancy of 51% after 1 year was achieved. A recurrence rate of 8% was observed for a follow-up of 2-11 years. Histological data demonstrated that the epithelium covering the ovary which is the mesothelium can invaginate in the ovarian cortex. Some of the invaginations were seen to be continuous with endometrial tissue, strongly suggesting the metaplasia theory in the pathogenesis of ovarian endometrioma.

The changes in uterine artery blood flow in women undergoing in-vitro fertilization cycles were studied throughout stimulation after gonadotrophin-releasing hormone (GnRH) desensitization. The data obtained showed that the uterine vascularity was related to hormonal changes. The GnRH agonist effect was seen only after the third week of administration, and the uterine perfusion was significantly (P = 0.002) improved by the oestradiol secretion. Human chorionic gonadotrophins increased the resistance index (RI) significantly (P = 0.0001) for a period of 48 h. Then the progesterone secretion modified the curve with a significant improvement in the uterine blood flow (P = 0.03). Comparison of the RI value 2 days before human menopausal gonadotrophin (HMG) commencement, in patients with and without pregnancy, showed a higher RI in patients who did not conceive but no difference was observed on the day of embryo transfer. The pregnancy rates were similar whatever the range of the RI observed. The data available so far suggest that haemodynamic parameters alone, detected by Doppler sonography, do not provide full information on endometrial receptivity on the day of embryo transfer. A resistance index > 0.79 before HMG commencement seems to indicate poor uterine vascularity and may necessitate an increase in the HMG doses to prevent endometrial immaturity.

A series of 231 cases of deep-infiltrating endometriosis of the rectovaginal septum is presented. Laparoscopic procedures with excision of deep fibrotic endometriotic nodules were performed in all cases. In three cases, the bowel lumen was entered. No other peri-operative complications were observed. Three cases of urinary retention were reported. The nodule resection resulted in considerable pain relief. Histologically, the rectovaginal nodule was similar to an adenomyoma. Indeed it was a circumscribed nodular aggregate of smooth muscle and endometrial glands. This form of disease must be considered as a specific disease which originates from the Mullerian rests present in the rectovaginal septum and we suggest that it be called 'rectovaginal adenomyosis'.

From July 1990 to April 1996, 500 laparoscopic supracervical (subtotal) hysterectomies (LASH) were performed. The technique and the advantages are described here. Because of the feasibility of this technique, the quick recovery of the patient and low rate of complications, this strictly laparoscopic approach must be widely considered when a hysterectomy is indicated and if there is no risk of remaining cervical cancer.

The considerable overlap of distributions of values for different parameters between control and ovarian hyperstimulation syndrome (OHSS) populations makes any single variable inefficient for risk prediction. Combinations of variables were studied in a discriminant function in order to increase predictivity and decrease the false negative rate. Such analyses were performed on two groups of in-vitro fertilization (IVF) patients: all OHSS cases (n = 128) (group A) and only severe OHSS cases (n = 92) (group B). Progressive introduction and automated stepwise selection of variables were applied to both groups. The best prediction (78.5%) was obtained in group A under post-oocyte retrieval conditions using log oestradiol, slope of log oestradiol increment, human menopausal gonadotrophin (HMG) dosage, number of oocytes retrieved and ratio of luteinizing hormone/follicle stimulating hormone (LH/FSH), in the formula. The corresponding false negative rate was 18.1%. However, effective prevention of OHSS implies the ability to withhold human chorionic gonadotrophin injection. Therefore a formula for pre-oocyte retrieval conditions was established yielding a prediction rate of 76.1% with a false negative rate of 18.1%. To be validated, such formulae have to be applied to another population of IVF cases used as a 'testing-set'.

Two progesterone presentations, a vaginal application of 90 mg progesterone per day (Crinone) or 300 mg progesterone administered orally (Utrogestan), were compared for luteal phase support of patients undergoing an in-vitro fertilization (IVF) procedure. A total of 283 patients were randomly allocated to either treatment. The treatment started within 24 h after the embryo transfer procedure and continued until day 30 in cases of implantation. Efficacy was assessed using the pregnancy and delivery rates. Safety was assessed through specific symptoms and usual safety monitoring. The pregnancy rates per transfer were not significantly different in the Crinone and Utrogestan groups at days 12 (Crinone 35.3%, Utrogestan 29.9%, P = 0.55), 30 (Crinone 28.5%, Utrogestan 25.0%, P = 0.61) and 90 (Crinone 25.9%, Utrogestan 22.9%, P = 0.69). No differences in the spontaneous abortion rates were seen thereafter. The delivery rates (number of deliveries per patient; Crinone 23.0%, Utrogestan 22.2%, P = 1.00), as well as the ratio of newborn babies per embryo transferred (Crinone 11.7%, Utrogestan 11.1%, P = 0.91), were not significantly different. Safety parameters were similar in both groups, except for drowsiness, which was more significantly frequent in the oral progesterone group than in the Crinone group at all time points. No serious adverse events were recorded in this study. The fact that Crinone matches the efficacy of the larger doses of progesterone used orally reflects an advantage of the transvaginal route of administration which avoids the metabolic inactivation of progesterone during its first liver pass.

Recently advanced computerized technology was applied to the investigation of morphometric, immunohistological and three-dimensional changes of the endometrial mucosa in order to evaluate quantitatively the effects of three doses of a new slow-release vaginal progesterone on the endometrium in post-menopausal women. A total of 20 menopausal women, deprived of ovarian function, were given oestrogen for 12 days and a combined therapy of oestrogen (administered orally) and progesterone for another 12 day period. Progesterone was administered vaginally through a new gel (Crinone) utilizing a bioadhesive, biocompatible polymer as a base to achieve a sustained release effect. An endometrial biopsy was taken before treatment, after oestrogen-only treatment and after the oestro-progestogen therapy. Before treatment, all the patients exhibited an atrophic endometrium. After oestrogen-only treatment, typical proliferative changes occurred: an increase in the endometrium thickness, an increase in the mitotic index, numerous cylinder-like glands and no coiled glands, and high concentrations of oestrogen receptors (ER) and progesterone receptors (PR). After the oestro-progestogen therapy, whatever the dose of progesterone given, a secretory transformation of the endometrial mucosa occurred, mitotic activity decreased significantly, more ramified and coiled glands were observed, and a decrease in PR content was noted in epithelial and stromal nuclei, and a decrease in PR content was also observed in epithelial nuclei but not in stromal nuclei. Accurate new techniques of image analysis have shown that crinone therapy could eliminate the proliferative effects of oestrogen treatment in post-menopausal women, despite doses as low as 45 mg of progesterone administered vaginally every other day. The results suggest that the sustained release effects of Crinone are clinically relevant.

For patients who are planning to have chemotherapy, radiotherapy or to undergo bilateral oophorectomy, loss of ovarian function will result in premature ovarian menopause and loss of fertility. For these women, although there is no successful method for the cryopreservation of human oocytes, ovarian tissue cryobanking is proposed with a view to its autotransplantation at a later date or the isolation and in-vitro maturation of oocytes. Embryo preservation is indeed not an option for single women and even for married women because delaying treatment for at least 2 months of in-vitro fertilization cycles is inappropriate and life-threatening. Following the success of animal experiments, there have been reports of ovarian cryopreservation for women having to receive chemotherapy and/or radiotherapy. We present four case reports of ovarian tissue cryobanking and review the consequences of chemotherapy and radiotherapy on gonadal function, as well as the indications for freezing ovarian tissue.

The role of transvaginal pulsed colour Doppler ultrasound in the assessment of ovarian vascularity was studied in 196 in-vitro fertilization (IVF) cycles. The changes in ovarian blood flow after gonadotrophin-releasing hormone agonist (GnRHa) down-regulation and human menopausal gonadotrophin (HMG) stimulation were determined. The data obtained showed that the ovarian blood flow was significantly improved by oestradiol secretion (P = 0.05) and human chorionic gonadotrophin (HCG) administration (P = 0.003). Folliculogenesis was affected by blood flow supply. The resistance index (RI) value was significantly different (P = 0.05) according to the duration of ovarian stimulation. Patients with a mean RI value >0.56 had a longer stimulation with a significantly lower mean number of oocytes retrieved (P = 0.01) despite the administration of a standard dose of HMG. The RI value is a good indicator of modifications in ovarian vascularization during stimulation. Doppler blood flow measurement could be used to determine the optimal timing for the beginning of HMG administration in patients undergoing ovarian stimulation after down-regulation for IVF treatment.

Adnexal torsion is a rare occurrence during pregnancy. Here we present a case of adnexal torsion during the 25th week of pregnancy, which was managed laparoscopically. The woman had achieved a successful twin pregnancy after in-vitro fertilization/intracytoplasmic sperm injection. She was admitted to the emergency department with acute abdominal pain. Abdominal ultrasound with colour Doppler mapping of the intra-ovarian blood flow showed adnexal torsion. Laparoscopic management was successfully carried out.Keywords: adnexal torsion/colour Doppler/laparoscopy/twin pregnancy

Adnexal torsion is a rare occurrence during pregnancy. Here we present a case of adnexal torsion during the 25th week of pregnancy, which was managed laparoscopically. The woman had achieved a successful twin pregnancy after in-vitro fertilization/intracytoplasmic sperm injection. She was admitted to the emergency department with acute abdominal pain. Abdominal ultrasound with colour Doppler mapping of the intra-ovarian blood flow showed adnexal torsion. Laparoscopic management was successfully carried out.

A combination of an extra-uterine and an intra-uterine pregnancy is defined as heterotopic pregnancy. An infertile patient, pregnant at her fourth in-vitro fertilization/embryo transfer attempt, was diagnosed at 21 weeks' gestation as having simultaneous abdominal and intra-uterine pregnancy. Expectant management under strict hospitalization was proposed and accepted by the couple, fetal assessment was by serial ultrasound evaluation of growth and amniotic fluid volume and by non-stress tests. Planned operative delivery was accomplished at 34 weeks' gestation. Both the mother and infants are alive and well.

Fertility following laparoscopic treatment of benign adnexal cysts without ovarian suture was studied retrospectively. Patients with endometriomas or who were previously infertile were excluded. Thirty-eight patients treated conservatively were included, 10 after partial resection of functional cysts, 23 after an ovarian cystectomy and six after treatment of a paraovarian cyst. One patient had two cysts. The overall intrauterine pregnancy rate was 92%; one patient had an ectopic pregnancy (2.6%). From these results, we conclude that fertility following laparoscopic treatment of adnexal cysts appears to be normal. Technical guidelines to improve laparoscopic cystectomy are proposed.

A combination of an extra-uterine and an intra-uterine pregnancy is defined as heterotopic pregnancy. An infertile patient, pregnant at her fourth in-vitro fertilization/embryo transfer attempt, was diagnosed at 21 weeks gestation as having simultaneous abdominal and intra-uterine pregnancy. Expectant management under strict hospitalization was proposed and accepted by the couple, fetal assessment was by serial ultrasound evaluation of growth and amniotic fluid volume and by non-stress tests. Planned operative delivery was accomplished at 34 weeks gestation. Both the mother and infants are alive and well.

Micromanipulation of mouse gametes with a commercially available compact laser microbeam system was studied. Both the normal in-vitro fertilization (IVF) group and the laser zona dissection (LZD) group were tested under normal (2X106 motile spermatozoa/ml) and low (500 000 motile spermatozoa/ml) insemination conditions. Subzonal insemination (SUZI) was also tried in a small group of gametes and the results were compared with those of the low insemination groups. Fertilization rates and blastocyst formation rates for the IVF and the LZD-treated groups were respectively 53 and 60% and 60 and 78%, which were not significantly different. However, under low insemination conditions, the results were significantly better in the LZD-treated group (58% fertilization rate and 83% blastocyst formation rate) compared to the results of the IVF group (33 and 48%) (P < 0.05). The SUZI-treated group showed the lowest fertilization rate (18%). No significant difference between the LZD and the IVF group was observed with respect to parthenogenetic activation. LZD has a beneficial effect on fertilization rates in cases of reduced sperm qualit.

The considerable overlap of distributions of values for different parameters between control and ovarian hyperstimulation syndrome (OHSS) populations makes any single variable inefficient for risk prediction. Combinations of variables were studied in a discriminant function in order to increase predictivity and decrease the false negative rate. Such analyses were performed on two groups of in-vitro fertilization (IVF) patients: all OHSS cases (n = 128) (group A) and only severe OHSS cases (n = 92) (group B). Progressive introduction and automated stepwise selection of variables were applied to both groups. The best prediction (78.5%) was obtained in group A under post-oocyte retrieval conditions using log oestradiol, slope of log oestradiol increment, human menopausal gonadotrophin (HMG) dosage, number of oocytes retrieved and ratio of luteinizing hormone/follicle stimulating hormone (LH/FSH), in the formula. The corresponding false negative rate was 18.1%. However, effective prevention of OHSS implies the ability to withhold human chorionic gonadotrophin injection. Therefore a formula for pre-oocyte retrieval conditions was established yielding a prediction rate of 76.1% with a false negative rate of 18.1%. To be validated, such formulae have to be applied to another population of IVF cases used as a ‘testing-set’.

A series of 231 cases of deep-infiltrating endometriosis of the rectovaginal septum is presented. Laparoscopic procedures with excision of deep fibrotic endometriotic nodules were performed in all cases. In three cases, the bowel lumen was entered. No other peri-operative complications were observed. Three cases of urinary retention were reported. The nodule resection resulted in considerable pain relief. Histologically, the rectovaginal nodule was similar to an adenomyoma. Indeed it was a circumscribed nodular aggregate of smooth muscle and endometrial glands. This form of disease must be considered as a specific disease which originates from the Mullerian rests present in the rectovaginal septum and we suggest that it be called ‘rectovaginal adenomyosis’.