Ethanol sclerotherapy: a treatment option for ovarian endometriomas before ovarian stimulation.

Several surgical treatment modalities have been described in cases of isolated or multiple ovarian endometriotic cysts. The aim of this preliminary study was to investigate and test the efficacy of ethanol sclerotherapy (EST) for recurrent endometriotic cysts, before ovarian stimulation in infertile patients with an adequate ovarian status. In the setting of a prospective comparative study, EST was proposed to 31 infertile patients with recurrence of ovarian endometriomas before inclusion in assisted reproduction cycles. Reproductive outcome was compared with that of patients who had previous laparoscopic cystectomy for recurrent endometriomas. The mean size of endometriomas treated with sclerotherapy was 38.6 +/- 11.2 mm in diameter. Ovarian cysts recurred in 12.9% of cases; at a mean time of 10 months after EST. Ovarian reserve and ovarian response to stimulation were better in the EST group than in the control group. Consequently, clinical and cumulative pregnancy rates of the study group were higher than those of the control group (48.3% versus 19.2%, P = 0.04; and 55.2% versus 26.9%, P = 0.03, respectively). Ethanol sclerotherapy may be a good alternative to surgical management of recurrent endometriotic cysts before assisted reproductive treatment. It could be advised for selected infertile patients.

Effect of growth hormone on oocyte competence in patients with multiple IVF failures.

In a preliminary, unpublished randomized study conducted in 2000 on 39 patients, including a placebo group, it was observed that the addition of growth hormone (GH) during ovarian stimulation in patients with poor-quality oocytes increased the pregnancy rate. However, the results were not statistically significant due to the small number of patients in each group. A protocol with 8 IU GH was tested in 291 patients with three or more previous failures of embryo transfer for no clearly identifiable reasons. The analysis was restricted to patients receiving either recombinant FSH or human menopausal gonadotrophin (HMG) (n = 245). They were compared retrospectively to all patients with three or more failures during the same period of time but stimulated only with recombinant FSH or HMG, without GH, in an observational study design. Co-stimulation with GH gave better results in terms of number of oocytes collected and embryos obtained. Pregnancy rate per retrieval was higher than in the control group (25.7% versus 18.2%, P < 0.01) and reached a level similar to the one observed in the study centre for the whole population. Ovarian stimulation associated with GH can be proposed for patients with a history of repeated assisted reproduction failures. An improvement of cytoplasmic competence is proposed as an explanation.

[Causes and clinical implications of sperm DNA damages]. / Causes et implications cliniques des altérations de l'ADN des spermatozoïdes.

Numerous recent studies involve DNA damages associated with poor fertilization rates, early embryo development defect, and poor quality of conceptus following Assisted Reproductive Technologies (ART). The authors denounce a particularly high rate of miscarriages and childhood cancer or dominant genetic mutations such as achondroplasia, Apert syndrome or aberrant gene imprinting such as Angelman and Beckwith Wiedeman syndromes. Gametes DNA defects have numerous origins which are difficult to determine; they are known to involve hypomethylation, oxydative stress and environmental factors.(adducts formation). DNA defect is also linked to a more or less delayed apoptotic phenomenon. Exposure to radiations or radiofrequency electromagnetic emissions can also induce DNA alterations into the spermatozoa of infertile men. Although the underlying mechanisms are unclear, these DNA defects have obvious consequences on reproduction of mammalian species. Detection of such anomalies before ART, are an important step toward developing strategies for clinical management according to the aetiology.

Dialogue between blastocyst hCG and endometrial LH/hCG receptor: which role in implantation?

The specific interaction of blastocyst-derived human chorionic gonadotropin (hCG) and endometrial LH/hCG-R constitutes a fundamental component of the molecular dialogue at the materno-fetal interface. From our observations and studies from other groups, hCG was indeed shown to play a significant role in implantation and tolerance of the embryo, decidual differentiation and remodeling, as well as in placentation. The profile pattern of LH/hCG-R expression by endometrial epithelium correlates with the theoretical timing of the implantation window. Studies are currently being conducted in assisted medical procreation and in an animal model of implantation to establish the index of LH/hCG-R expression as a new biomarker of uterine receptivity for embryo implantation.

[Indications for IMSI]. / Les indications de l'IMSI.

ICSI failures (essentially fertilization and implantation failures) can be due to the quality of the oocytes, the spermatozoon injected and its manipulation, uterine factors and paternal factors, such as DNA fragmentation of the spermatozoa. Pre-selection of the spermatozoon is the crucial phase for ensuring successful ICSI. The characteristics of the sperm must be checked under the microscope at a magnification of x 6600 as certain abnormalities, in particular nuclear vacuoles, cannot be seen at x 300. In our centre, we conducted a study on 72 patients which showed that with more than 30% of fragmented DNA, neither implantation or birth was achieved using ICSI. Performing IMSI on the same patients allowed us to obtain implantation rates of 17.4% with 30 to 40 % of fragmented DNA and of 33.3% above 40%. Births were achieved in 17.4% and 28.6% of cases respectively. IMSI has the advantage of allowing extremely careful selection of the spermatozoon microinjected, so that it is of normal shape, with the least vacuoles possible and a low DNA fragmentation rate. It is, however, a complicated technique that cannot be routinely performed.

[Oocyte quality and ovarian reserve]. / Peut-on prévoir la qualité ovocytaire par la réserve ovarienne?

No clinical or biological parameter can predict oocyte quality. In women with uncertain ovarian function, antral follicle count and serum anti-Müllerian hormone/Müllerian-inhibiting substance appear to be more discriminatory markers of ovarian reserve and assisted reproductive technology outcome. FSH levels should be correlated with estradiol levels, antral follicle count, and patient age.

[Ovarian endometriomas: Effect of laparoscopic cystectomy on ovarian response in IVF-ET cycles]. / Endométriomes ovariens: effet de la kystectomie laparoscopique sur la réponse ovarienne en fécondation in vitro.

OBJECTIVE: To investigate the follicular response to controlled ovarian hyperstimulation (COH) in IVF-ET cycles after laparoscopic ovarian cystectomy for large endometriomas. PATIENTS AND METHODS: In the set of a retrospective controlled study, the medical records of 113 infertile women who underwent IVF-ET cycles after laparoscopic surgery were reviewed. The study group (A) consisted of 63 patients with severe pelvic endometriosis and endometrioma excision. The control group (B) consisted of 50 infertile patients with mild or minimal endometriosis. Interventions were laparoscopic ovarian cystectomy in the study group, and COH in both groups. RESULTS: Groups A and B were not different in terms of epidemiologic data. The total numbers of recruited follicles (9.1+/-3.3 vs 10.6+/-4.2; P = 0.001), mature follicles (> or =16 mm) (4.2+/-1.7 vs 4.8+/-2.2; P = 0.04), mature oocytes retrieved (5.8+/-3.8 vs 7.4+/-4.6; P = 0.02), and fertilization rate (48.9+/-34.9 vs 61.8+/-32.1%; P = 0.02) observed in group A were lower than those observed in group B, respectively. While the mean number of rFSH ampoules (75 IU) was increased in group A (38.1+/-20.4) compared to group B (29.3+/-16.4; P = 0.004), cumulative pregnancy rates were similar in both groups (27.5+/-8.8% vs 37.2+/-10.6%; P = 0.37). DISCUSSION AND CONCLUSIONS: Ovarian response was reduced during IVF-ET cycles in patients with history of severe endometriosis and laparoscopic excision of endometriomas compared to women with mild or minimal endometriosis without ovarian surgery.

[FSH is a limiting factor]. / FSH facteur limitant.

FSH concentrations obtained early in the follicular phase is a good predictive factor of ovarian response for assisted reproductive treatment. Nevertheless, FSH levels should be correlated with estradiol levels, antral follicle count and patient age. A history of elevated basal FSH levels in patients under the age of 40 years predicts a lower oocyte yield in IVF cycles but does not translate to either lower pregnancy or implantation rates. In women with uncertain ovarian function, antral follicle count and serum antimullerian hormone/mullerian-inhibiting substance appear to be more discriminatory markers of assisted reproductive technology outcome.

[Assisted reproductive technologies after conservative management of borderline or invasive ovarian tumours]. / Assistance médicale à la procréation après traitement conservateur d'une tumeur de l'ovaire invasive ou à la limite de la malignité.

OBJECTIVE: Ovulation induction, the usual resort of Assisted Reproductive Technologies (ART), has been suspected of carrying a responsibility in the genesis of ovarian tumours. For patients with a borderline or invasive ovarian tumour, treated by conservative surgery and desiring to become pregnant, the problem is thus of a possible resort to the Assisted Reproductive Technologies. PATIENTS AND METHODS: This is a multicenter, national and retrospective study. 40 operated patients between January 1971 and January 2001 have been included. 27 patients (67.5%) had a borderline tumour, 10 (25%) a non-epithelial tumour (germinal or stromal) and 3 (7.5%) an epithelial invasive carcinoma. All these patients have benefited from a conservative surgical management of fertility. The Assisted Reproductive Technologies were simple stimulation for 5 women and IVF for the 35 others. The effectiveness and the risks of Assisted Reproductive Technologies have been estimated respectively by the number of pregnancies obtained and the recurrence rates. RESULTS: With a global follow-up of 372 months (January 1971: date of the primary surgical procedure--June 2002: closing of the study), 17 patients have obtained 17 pregnancies with the Assisted Reproductive Technologies, rate of 42.5% (17/40): 1 spontaneous abortion, 16 delivery with 23 children (triple pregnancies and 3 twin pregnancies). 3 patients treated for a borderline tumour have had a recurrence after induction of ovulation. Among the 40 patients, no one presented an evolved disease at the last news. The patients who had a recurrence had a delay to begin the Assisted Reproductive Technologies significantly lower than the patients who had no recurrence. DISCUSSION AND CONCLUSION: The assisted reproductive technologies for patients who had been treated for a borderline or invasive ovarian tumour, and who were infertile in spite of conservative management, have allowed 42.5% of these women to obtain a pregnancy and does not seem to increase significantly the risk of recurrence.

Human chorionic gonadotropin and growth factors at the embryonic-endometrial interface control leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) secretion by human endometrial epithelium.

BACKGROUND: The elucidation of the molecular mechanisms by which the embryo contributes to its implantation is an area of extensive research. The main objective of this study was to investigate the pattern of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) secretion by human endometrial epithelium, and their regulation by human chorionic gonadotropin (hCG) and other growth factors present at the embryonic-endometrial interface. METHODS: Endometrial epithelial cells (EEC) were isolated from biopsies collected at both proliferative and secretory phases of fertile women. RESULTS: HCG (1-50 IU/ml) increased LIF secretion by EEC cultures derived from follicular phase (up to 285+/-75%) or from secretory phase (up to 212+/-16%). In contrast, hCG reduced IL-6 secretion by EEC in both phases. The hCG/LH receptor gene was transcribed by EEC as evidenced by RT-PCR. Insulin-like growth factors 1 and 2 increased LIF secretion by EEC. Transforming growth factor beta1 stimulated LIF and reduced IL-6 secretion. CONCLUSIONS: Through hCG, the blastocyst may be involved in the control of its implantation (via an increase of proimplantatory LIF) and tolerance (via an inhibition of proinflammatory IL-6). Other growth factors present at the embryonic-endometrial interface are also involved in the control of LIF and IL-6 endometrial secretion.