Respective efficacy of gonadotrophins should be the heart of the debate.

Recombinant gonadotrophins offer future advances in reproductive medicine. It is questionable whether they produce more pregnancies than urinary gonadotrophins. No doubt future advances will permit this goal, but this has not yet been attained.

Time to revolutionize the triggering of ovulation.

Methods used for ovarian stimulation constantly change with advances in gonadotrophin therapy. In this Commentary, an appeal is made for more attention to the use of LH for the induction of ovulation. Its typical characteristics during the LH surge are finely balanced to induce normal ovulation and luteinization. It does not induce ovarian hyperstimulation, for example. The recent commercial availability of recombinant LH (LHr) offers a chance of escaping from the use of urinary human chorionic gonadotrophin (HCG) and its varied forms such as those with a shorter half-life. It should also avoid the weakly effective bursts of FSH and LH and weak luteal phases released associated with the use of gonadotrophin-releasing hormone agonists. Currently, large dosages of LHr are needed to match the endocrine events typical of inducing ovulation by the endogenous LH surge. In the interests of patients' safety and improved forms of luteal phase endocrinology, research should be devoted to improving the properties of rLH to make it induce surges similar to endogenous discharges. This would replace the current use of HCG to induce ovulation, with its attendant risks of ovarian hyperstimulation and luteal phase anomalies.

Luteal phase defects following agonist-triggered ovulation: a patient-dependent response.

The luteal phase (LP) of patients receiving triptorelin 0.1 mg to trigger ovulation was studied. Patients not pregnant in the first cycle with 0.1 mg were randomized into different groups for a second cycle: 0.1 mg again for patients who experienced a normal LP (group 1); patients affected with LP disorders were randomized into the following groups: 0.1 mg again (group 2); increasing dosage of triptorelin 0.5 mg once (group 3) or 0.1 mg three times (group 4); luteal support either with oral micronized progesterone (group 5) or human chorionic gonadotrophin (HCG) 1500 IU (group 6). Ovulation occurred in all cycles, but an inadequate LP was observed in 34.4% of the non-conceptional cycles. Patients demonstrating a normal LP as well as those affected with luteal disorders in their first cycle showed the same luteal pattern in their consecutive cycles triggered in the same way. In defective LP patients, increasing or repeating triptorelin doses did not restore the luteal phase or the pregnancy rate, both returning closer to normal after luteal support. Defective LP observed after agonist-triggered ovulation do not occur at random; therefore this patient-dependent response may be related to the personal characteristics of each patient's pre-ovulatory physiological surge profile.

[Introduction of the antagonist: on a determined day or depending on follicular growth?]. / Introduction de l'antagoniste: à jour fixe ou selon la croissance folliculaire?

Introduction of the antagonist: on a determined day or depending on follicular growth? GnRH antagonists prevent LH surge in IVF cycles. GnRH antagonist can be administrated at a fixed day (day 6) or according to mean follicle size and estradiol levels (flexible regimen). Less monitoring is required for IVF cycles with the fixed regimen. For the flexible regimen, GnRH antagonist should be initiated on the day when the leading follicle reaches 14 mm diameter. Flexible regimen should decrease total antagonist and gonadotropin doses. Similar pregnancy rates are observed between the fixed and the flexible GnRH antagonist regimens.

[Revisiting the clomifene-gonadotropin protocol in IVF with the use of a GnRH antagonist]. / Réhabilitation du protocole clomiphène-gonadotrophines en FIV par l'utilisation d'un antagoniste du GnRH.

OBJECTIVE: To assess the ability of GnRH antagonists to prevent LH surges during superovulation for IVF in classical stimulation protocols with clomiphene and gonadotropins. PATIENTS AND METHODS: Fifty-eight patients were treated with clomiphene (100 mg daily for 5 days starting on cycle day 2) and gonadotropins (225 UI HMG on cycle days 5, 7 and 9), with monitoring starting on cycle day 10. Cetrorelix, 0.25 mg, was administered daily when dominant follicle diameter reached 18 mm and/or plasma estradiol levels 800 pg/ml. RESULTS: No premature LH surge was observed during the 48 stimulation cycles completed. The pregnancy rate was 20.8% per punction and 25.6% per transfer, and there was no clinical ovarian hyperstimulation syndrome in these series. CONCLUSIONS: Cetrorelix, 0.25 mg, optimizes the classical stimulation with clomiphene and gonadotropins by preventing LH surges; the so-completed protocol yields acceptable pregnancy rates with lower hormone quantities and reduced risks of ovarian hyperstimulation, and becomes a convenient choice when "softer" treatments for IVF are considered.

[Comparison of different protocols of ovulation induction, by GnRH agonists and chorionic gonadotropin]. / Comparaison de différents protocoles de déclenchement de l'ovulation, par agonistes du GnRH et gonadotrophine chorionique.

OBJECTIVE: The aim of this study was to determine the best way of using a gonadotropin-releasing hormone agonist (GnRHa) for triggering ovulation and to analyse the reasons for short luteal phases. MATERIALS AND METHODS: Thirteen different regimens of GnRH-a administration were used to trigger ovulation using different dosages and either one, two or three administrations: triptorelin, buserelin spray, buserelin subcutaneously, leuprolide and nafarelin in 231 treatment cycles. Pregnancy rate and luteal phase duration were compared with those of a control group for whom ovulation was triggered with hCG. RESULTS: Ovulation with supraphysiologic elevation of both FSH and LH was achieved in the 13 GnRHa groups. For the five main groups analysed, GnRHa produced shorter and inadequate luteal phases than did hCG but no difference was found between agonists. Pregnancy rates were not statistically different between the agonist groups or in comparison with the hCG group. CONCLUSION: The use of GnRHa to trigger ovulation is efficient, despite short luteal phases, and has proven its utility in comparison with hCG. As the different modes of stimulation appear to yield comparable results, the cost of treatment should be a significant element to take into consideration.

Prospective, randomized, controlled study of in vitro fertilization-embryo transfer with a single dose of a luteinizing hormone-releasing hormone (LH-RH) antagonist (cetrorelix) or a depot formula of an LH-RH agonist (triptorelin).

OBJECTIVE: To confirm the value of a single dose of 3 mg of cetrorelix in preventing the occurrence of premature LH surges. DESIGN: Multicenter randomized, prospective study. SETTING: Reproductive medicine units. PATIENT(S): Infertile patients undergoing ovarian stimulation for IVF-ET. INTERVENTION(S): A single dose of 3 mg of cetrorelix (Cetrotide; ASTA Medica, Frankfurt, Germany) (115 patients) was administered in the late follicular phase. A depot preparation of triptorelin (Decapeptyl; Ipsen-Biotech, Paris, France) was chosen as a control agent (39 patients). Ovarian stimulation was conducted with hMG (Menogon; Ferring, Kiel, Germany). MAIN OUTCOME MEASURE(S): Premature LH surges (LH level >10 IU/L), progesterone level greater than 1 ng/L, and IVF results. RESULT(S): No LH surge occurred after cetrorelix administration. The patients in the cetrorelix group had a lower number of oocytes and embryos. The percentage of mature oocytes and fertilization rates were similar in both groups, and the pregnancy rates were not statistically different. The length of stimulation, number of hMG ampules administered, and occurrence of the ovarian hyperstimulation syndrome were lower in the cetrorelix group. Tolerance of cetrorelix was excellent. CONCLUSION(S): A cetrorelix single-dose protocol prevented LH surges in all patients studied. It compares favorably to the "long protocol" and could be a protocol of choice in IVF-ET.

[Difficult embryo transfers: contribution of echography]. / Transferts d'embryons difficiles: l'apport de l'échographie.

The aim of this retrospective study is to compare the results of embryo transfer in IVF without or after cervical dilatation, and trans-myometrial trans-vaginal transfer and after ultrasound-guided transfer. From 1989 to 1996 we have performed 4,355 embryo transfers to obtain 1,115 pregnancies. The results were 25.6% pregnancy by transfer and 10.9 embryos to start a pregnancy. During this time 281 transfers were appreciated as difficult or impossible and a cervical dilatation was done. We obtain 17.4% pregnancies by transfer with 16.5 embryos per pregnancy. We also practiced for the same indication 50 transmyometrial-transvaginal transfers. The result was 18% pregnancy by transfer and 16 embryos to start a pregnancy. In 1997 we have stopped cervical dilatations to prefer in these indications ultrasound-guided embryo transfer. 74 transfer were performed with this method to obtain 28.4% pregnancies per transfer and 9.9 embryos to start one pregnancy. This results are compared to a subgroup of women 38 years old or less, with a normal partner's sperm and in witch two embryos or more were transferred. At the end we think that the use of ultrasonography for embryo transfer is benefit in IVF program.

A comparative prospective study of a chronic low dose versus a conventional ovulation stimulation regimen using recombinant human follicle stimulating hormone in anovulatory infertile women.

The efficacy and safety of a chronic low dose (group A) and a conventional (group B) stimulation regimen of recombinant human follicle stimulating hormone (r-HFSH) were compared in 103 WHO Group II infertile women with clomiphene citrate-resistant anovulation. Mono- or bifollicular development was induced in 88.1% of patients in group A compared with 76.1% in group B. Ovulation and pregnancy rates were higher in group A (71.4% and 33.3%, respectively) than in group B (63.0% and 20%), but these differences were not statistically significant. Additionally, the total number of follicles that were >10 mm diameter was lower in group A than group B (3.0+/-2.6 versus 6.3+/-6.5; P < 0.0001), as was the oestradiol concentration (504+/-477 pg/ml versus 988+/-740 pg/ml; P < 0.03). The median dose of FSH (75 IU ampoules) used per cycle was 11 ampoules in group A and 12.5 in group B. In terms of the incidence of ovarian hyperstimulation syndrome, no differences were recorded between the two groups. The results demonstrated that r-HFSH is effective and safe in both these treatment protocols. The chronic low dose regimen was associated with a trend towards a higher rate of mono- or bifollicular development, without jeopardizing the incidence of pregnancy.

Ongoing pregnancies after intracytoplasmic injection using cryopreserved testicular spermatozoa.

We report two clinical pregnancies occurring after intracytoplasmic sperm injection (ICSI) using cryopreserved spermatozoa obtained from testicular biopsy, made in two different infertility situations in our clinic. The first patient showed a secretory azoospermia associated with elevated serum follicular stimulating hormone (FSH) level and spermiogenesis maturation arrest. The second patient was affected by azoospermia resulting from bilateral epididymal obstruction. Spermatozoa present in the wet preparation of testicular biopsy made on the day of scrotal exploration were cryopreserved within the testicular tissue for both men. Intracytoplasmic injections were performed at a later date, using spermatozoa prepared from frozen-thawed tissues. In each case, three embryos were obtained and transferred in utero. The transfers resulted in a twin pregnancy for the first case, and in a singleton pregnancy for the second. Living foetuses were seen in the ultrasound scan at the 7th week and both pregnancies are proceeding to date beyond 30 weeks without complications.

[Age and fertility: value of endometrial co-cultures]. / Age et fertilité: apport des cocultures sur cellules endométriales.

Embryo coculture system may contribute to understand the mechanisms underlying the decrease of fertility with aging. We report here our experience of coculture on maternal endometrial cells and histology of endometrial biopsy in 90 patients with repeated failures of implantation. Histology dating failed to find any age related changes. In coculture system, it is obvious that embryo viability diminishes with aging, but for equal embryonic quality, the maternal age does not interfere significantly on pregnancy rate. Anyway the number of first trimester abortions seems higher in older women. Coculture system emphasizes the major role of oocyte aging in the decrease of fertility and may be useful to establish a prognostic in IVF for older patients.

Coculture of embryos on homologous endometrial cells in patients with repeated failures of implantation.

OBJECTIVE: To evaluate the value of coculture of embryos on endometrial cells in patients with repeated failures of implantation. DESIGN: A retrospective comparison of pregnancy rates between IVF-ET with coculture and standard culture methods. PATIENTS: Ninety patients with repeated failures of transfer (range 4 to 11) underwent IVF-ET for a variety of disorders. METHOD: Embryos were cocultured on homologous endometrial cells and transferred on day 4 after retrieval of oocytes. RESULTS: The overall pregnancy rate for these patients was 21% per transfer versus 8% in previous IVF-ET cycles. A higher percentage (28%) was obtained for women < 39 years of age or on transfer of at least one morula (32.5% pregnancy per transfer). CONCLUSION: Coculture of embryos on homologous endometrial cells is both safe and ethical. It appears to be a valuable approach for the selection of a good quality embryo before transfer. The technique should prove to be of benefit to patients with repeated failures of implantation and also may be of value for assessing the respective responsibility of endometrium and embryo in these repeated failures. However, the mechanisms underlying this improvement need to be determined to simplify the procedure.

[Therapeutic induction of ovulation: towards the replacement of hCG with LH]. / Le déclenchement thérapeutique de l'ovulation: vers le remplacement de l'hCG par la LH.

Ovulation has exclusively been triggered with Human Chorionic Gonadotropin (hCG) since the earlier times of follicular stimulation with Pregnant Mare Serum Gonadotropins (PMSG). hCG was chosen in regard of its LH-like effect, when isolated or purified human LH was not available. hCG, however, is not the physiologic hormone for ovulation triggering and shows many discrepancies in pharmacokinetics and bio-availability with LH, accounting for the permanent risk for ovarian hyperstimulation syndrome (OHSS) following hCG administration. Human recombinant LH should become available in the coming years, but it is at present possible to trigger ovulation in hMG--stimulated patients with their own pituitary LH, using a short-acting GnRH agonist. Literature shows that this method of triggering ovulation in in vitro fertilization (IVF) cycles as well as in non IVF cycles results in a satisfactory ovulatory process and pregnancy rates comparable to those observed following hCG administration. More over, triggering ovulation with endogenous LH considerably reduces the risks for OHSS, and perhaps for multiple pregnancies. Optimum posology for each GnRH agonist available remains to be evaluated to minimize the occurrence of short luteal phases following ovulation triggering with endogenous LH.

[Treatment using laparoscopic surgery of dermoid cysts. Apropos of a series of 33 cysts]. / Traitement par coeliochirurgie des kystes dermoïdes. A propos d'une série de 33 kystes.

Laparoscopy is a surgical method which is now widely used for the treatment of ovarian cysts. The authors wish to present their experience concerning the management and treatment of dermoid cysts or dysembryomas since these lesions embody all the problems persisting in this field. They report 33 cases exclusively treated by laparoscopic surgery in a series of 407 adnexal cysts treated over a 4-year period (April 1988 to April 1992). As regards diagnosis, the principal difficulty is not to miss the odd malignant lesion (1 to 2%) encountered mainly in older women. Technically, the most delicate stage in the operation is extraction of the cyst, especially when it is large and has an important solid component. Provided all precautions are taken in the diagnosis and the operative technique, this new method seems to be quite acceptable as it enables women who carry these lesions, which require excision, to benefit from the well-known advantages of laparoscopic surgery.

[Ovulation induction by endogenous LH released by the administration of an LHRH agonist after follicular stimulation for in vitro fertilization]. / Déclenchement de l'ovulation par la LH endogène libérée par l'administration d'un agoniste de la LHRH après stimulation folliculaire pour fécondation in vitro.

Sixty-seven patients whose ovulation was stimulated following a protocol of Clomiphene Citrate/HMG in order to carry out in vitro fertilisation were divided randomly in to two groups. In the first group ovulation was provoked by giving 10,000 IU HCG IM, but in the other group ovulation was provoked by releasing endogenous LH after the administration of Triptoreline in a dose of 0.1 mg in a dose subcutaneously three times in one day at 8 hour intervals. The number of oocytes recovered, cleavage and embryo transfer were compared between the two groups over 48 cycles. The number of conceptions was statistically significantly higher in the group that had triptoreline (28%) as compared with 17.4% pregnancies in the other group (p less than 0.01). These figures confirm that the endogenous LH surge provoked by giving an LHRH agonist can cause adequate final oocyte maturation. This property which is associated with a very low risk of hyperstimulation, should make it possible to stimulate ovulation when it is not used for IVF and so replace the usual injection of chorionic gonadotrophins.