B. Hedon

Ovarian stimulation by a combination of a gonadotropin-releasing hormone agonist and gonadotropins for in vitro fertilization

In the first of two studies, 20 patients were selected on the basis of tubal infertility and were randomly assigned to two groups receiving different ovarian stimulation protocols. In group A, 10 patients were given follicle-stimulating hormone (FSH), FSH was continued until the criteria for human chorionic gonadotropin (hCG) administration were satisfied. In group B, 10 patients received Buserelin (0.3 ml twice a day subcutaneously) for 14 days to induce pituitary desensitization. Stimulation with FSH was then started, and Buserelin treatment was continued until hCG administration. In the second study, patients were included if they had had at least two previous attempts at ovarian stimulation that failed to reach the stage of follicular aspiration. Ovarian stimulation was conducted with a combination of Buserelin and human menopausal gonadotropin. Use of the gonadotropin-releasing hormone (GnRH) agonist in in vitro fertilization increased the number of oocytes collected, the fertilization rate, the length of the luteal phase and the pregnancy rate. The GnRH agonist also contributed to a generally better ovarian response in patients whose estradiol production had previously responded poorly to conventional ovarian stimulation protocols.

Effects of cigarette smoking on reproduction

BACKGROUND Cigarette smoking is associated with lower fecundity rates, adverse reproductive outcomes and a higher risk of IVF failures. Over the last few decades, prevalence of smoking among women of reproductive age has increased. This review focuses on current knowledge of the potential effects of smoke toxicants on all reproductive stages and the consequences of smoke exposure on reproductive functions. METHODS We conducted a systematic review of the scientific literature on the impact of cigarette smoking and smoke constituents on the different stages of reproductive function, including epidemiological, clinical and experimental studies. We attempted to create hypotheses and find explanations for the deleterious effects of cigarette smoke observed in experimental studies. RESULTS Cigarette smoke contains several thousand components (e.g. nicotine, polycyclic aromatic hydrocarbons and cadmium) with diverse effects. Each stage of reproductive function, folliculogenesis, steroidogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and uterine myometrium is a target for cigarette smoke components. The effects of cigarette smoke are dose-dependent and are influenced by the presence of other toxic substances and hormonal status. Individual sensitivity, dose, time and type of exposure also play a role in the impact of smoke constituents on human fertility. CONCLUSIONS All stages of reproductive functions are targets of cigarette smoke toxicants. Further studies are necessary to better understand the deleterious effects of cigarette smoke compounds on the reproductive system in order to improve health care, help to reduce cigarette smoking and provide a better knowledge of the molecular mechanisms involved in reproductive toxicology.

Gene expression profile of human endometrial receptivity: comparison between natural and stimulated cycles for the same patients

BACKGROUND The adjunction of exogenous hormones for controlled ovarian stimulation (COS) may alter endometrial receptiveness. In order to identify the genes misregulated under COS, we compared the endometrium gene expression profiles, from the same patients, in a natural cycle and in a subsequent COS cycle. METHODS For the same normal-responder patients (n = 21), endometrial biopsies (n = 84) were collected during the pre-receptive (LH + 2) and receptive stages (LH + 7) of a natural cycle and, subsequently, on oocyte retrieval day (hCG + 2) and on transfer day (hCG + 5) of a stimulated cycle. Samples were analyzed using DNA microarrays. Gene expression profiles and biological pathways involved in endometrial receptivity were analyzed. RESULTS Although endometrium transition profiles from pre-receptive to receptive phases are similar between patients, COS regimens alter endometrial receptivity in comparison with natural cycle. Under COS conditions, two endometrial profiles were identified and were associated either with a moderately altered receptivity profile for the majority of the patients or a strongly altered profile for a sub-category of patients. The receptive endometrium transcription profile under COS was defective for biological functions such as TGFbeta signaling, leukocyte transendothelial migration and the cell cycle. CONCLUSIONS Gonadotrophin treatments in COS cycles led to disruptions of the transcriptional activation of genes involved in normal endometrial receptivity. We propose that when the receptiveness of the endometrium is seriously compromised by the COS protocol, fresh embryo replacement should be cancelled, the embryo frozen and thawed embryo replacement should be performed under natural cycles.

Complex chromosomal rearrangements: origin and meiotic behavior

BACKGROUND Complex chromosomal rearrangements (CCRs) describe structural rearrangements, essentially translocations, involving at least three breakpoints on two or more chromosomes. Although they are rare in humans, their clinical identification is important since CCR carriers can display various phenotypes which include phenotypically normal subjects, infertile males and patients with mental retardation and/or congenital abnormalities. The rearrangement can be de novo or familial. The use of fluorescent in situ hybridization assays and molecular techniques for the characterization of CCRs have indicated that the rearrangements could be more complex than initially assumed. Accumulating data have revealed that the mechanisms underlying the genesis of CCRs remain elusive. METHODS We performed a large PubMed search in order to summarize the current knowledge in this field and address important aspects of CCR formation and meiotic behavior, highlighting the complexity of these rearrangements at the chromosomal and genomic level. RESULTS The review of published data indicates that the complexity of CCRs is becoming increasingly known, thanks to the application of more and more efficient molecular techniques. These approaches have allowed the precise sequence analysis of breakpoints and the identification of insertions, deletions, inversions and recombination events. New models have been proposed for the formation of CCRs, based on replication-based mechanisms and specific sequence elements. Their meiotic behavior has been discussed in the light of these new molecular data. CONCLUSIONS Despite the increasing understanding of the mechanisms involved in their genesis, CCRs arise as unique, complex events for which the genetic and reproductive counseling of carriers remains a challenge.

Does previous salpingectomy improve implantation and pregnancy rates in patients with severe tubal factor infertility who are undergoing in vitro fertilization? A pilot prospective randomized study

OBJECTIVE To evaluate the implantation rate and pregnancy rate (PR) in patients with severe tubal factor infertility who were undergoing IVF. Patients who had undergone salpingectomy were compared with those who had not. DESIGN A prospective randomized study. SETTING A department of obstetrics and gynecology at a university hospital. PATIENT(S) Thirty patients who previously had undergone salpingectomy and 30 patients who had not undergone salpingectomy before IVF treatment. INTERVENTION(S) Laparoscopy with or without salpingectomy followed by IVF with the use of combined GnRH agonist and hMG therapy in a long stimulation protocol. MAIN OUTCOME MEASURE(S) Embryo implantation rate and ongoing PR per transfer. The cumulative PRs were compared for the two groups of patients. RESULT(S) After the first IVF attempt, the implantation rate was 10.4% in the group with salpingectomy and 4.6% in the group without salpingectomy. For all IVF attempts, the respective embryo implantation rates in the two groups were 13.4% and 8.6%. The ongoing PR per transfer was 34.2% in the group with salpingectomy compared with 18.7% in the group without salpingectomy. After four IVF attempts, the probability of becoming pregnant was greater in the group of patients with salpingectomy (75%) than in the group without salpingectomy (63%). CONCLUSION(S) Previous salpingectomy in patients with severe tubal factor infertility who are undergoing IVF seems to increase the embryo implantation rate and the PR per cycle of IVF. This monocentric study must be followed by other similar studies to allow for a metaanalysis and confirm this clear trend with definitive evidence.

Integrated summary of ORTHO EVRA™/EVRA™ contraceptive patch adhesion in varied climates and conditions.

OBJECTIVE To assess the adhesive reliability of the contraceptive patch (Ortho Evra/Evra). DESIGN Pooled data of 3,319 women from three contraceptive studies of up to 13 treatment cycles; a subset of 325 women of the pooled data from warm and humid climates; and 30 women from a three-period, crossover exercise study. SETTING 184 centers. PATIENT(S) 3,349 healthy women. INTERVENTION(S) In the contraceptive studies, each treatment cycle consisted of three consecutive 7-day patches (21 days) followed by one patch-free week. During each treatment period in the exercise study, women wore the patch for 7 days and participated in one of six activities (normal activity, excluding bathing; sauna; whirlpool; treadmill; cool-water immersion; or a combination of activities) each day at a supervised health center. MAIN OUTCOME MEASURE(S) Patch adhesion. RESULT(S) In the contraceptive studies, 4.7% of patches were replaced because they fell off (1.8% [1,297 of 70,552 patches]) or became partly detached (2.9% [2,050 of 70,552 patches]); patch replacement rates in centers from a warm, humid climate were 1.7% (85 of 4,877 patches) and 2.6% (128 of 4,877 patches), respectively. Only one of 87 patches (1.1%) completely detached in the exercise study. CONCLUSION(S) The reliability of adhesion of the contraceptive patch is excellent and consistent across all studies; only 1.8% and 2.9% of patches required replacement due to complete or partial detachment, respectively. Heat, humidity, and exercise do not affect adhesion.

Hemostasis parameters during ovarian stimulation for in vitro fertilization: Results of a prospective study

OBJECTIVE To evaluate the effect of IVF-ET on the hemostatic system. DESIGN Prospective clinical study. SETTING Apparently healthy age-matched women of the hospital staff at various stage of the menstrual cycle. PATIENT(S) Twenty-five women involved in a IVF-ET program at the Department of Obstetrics and Gynecology, Montpellier University Hospital. INTERVENTION(S) Twenty-six hemostasis parameters evaluated repeatedly in patients undergoing IVF-ET. MAIN OUTCOME MEASURE(S) Blood cell-dependent hemostasis parameters and plasmatic coagulation factors, determined at pituitary desensitization, maximal E2 level, and P plateau. RESULT(S) Activation of the hemostatic system is evidenced at the P plateau, when D-dimers and fragments 1 + 2 of the prothrombin levels rose dramatically. At E2 peak, no significant modification of hemostasis markers was noted. CONCLUSION(S) The present results indicate that ovarian hyperstimulation may induce hemostasis activation at the P plateau. The role of supraphysiologic sex hormone levels on the hemostatic system requires further investigation.

Does transvaginal hydrolaparoscopy render standard diagnostic laparoscopy obsolete for unexplained infertility investigation

OBJECTIVE To evaluate the feasability of transvaginal hydrolaparoscopy in infertile patients undergoing basic infertility investigations, and to determine its usefulness in comparison with standard laparoscopy. MATERIALS AND METHODS Twenty-three unexplained infertile women were prospectively included. Selected patients had no history of pelvic disease or previous pelvic surgery and had normal findings on gynecological examination and vaginal sonography. The patients received general anesthesia and underwent the transvaginal hydrolaparoscopy immediately prior to a standard laparoscopy by a different operator. The main outcome measures were the rate of successful access to the pouch of Douglas, the duration of the procedure, and the rate of complications. In order to compare the accuracy of the transvaginal hydrolaparoscopy to the standard laparoscopy, findings in terms of tubal pathology, endometriosis, and adhesions were analyzed. RESULTS The successful rate of access to the pouch of Douglas was 95.7%. The rate of complications was 4.3%. The mean duration of the transvaginal hydrolaparoscopy procedure was 8 min. The concordance between transvaginal hydrolaparoscopy and laparoscopy for pelvic cavity examination was statistically significant (k=0.57, P=0.02). In 40.9% of cases, the transvaginal hydrolaparoscopy procedure has shown a normal pelvic examination confirmed by laparoscopic diagnosis. According to the findings by laparoscopy, transvaginal hydrolaparoscopic diagnosis was correlated well in 81.8% of cases. When transvaginal hydrolaparoscopy showed pathological findings, there were no normal laparoscopies. Pathological laparoscopies were found in 18.2% of the normal transvaginal hydrolaparoscopies. CONCLUSION The transvaginal hydrolaparoscopy is a reproducible and safe method to investigate the pelvis and its structures. The diagnostic accuracy of the transvaginal hydrolaparoscopy suggests that more than 40% of standard laparoscopies for unexplained infertility could be avoided.

Evaluation of Endometrial Inflammation by Quantification of Macrophages, T Lymphocytes, and Interleukin-1 and -6 in Human Endometrium

Purpose:Our purpose was to determine the impact of endometrial inflammation on fertility.Methods:The study population included 49 women: 5 women bearing an intrauterine device, 33 sterile patients, and 11 fertile women. Endometrial biopsies were performed between day 17 and day 21 of the cycle. Immunostaining was performed with an ABC kit. Monoclonal antibodies were CD68 for macrophages, CD3 for T lymphocytes, and B-E8 for interleukin (IL)-6; IL-1α and IL-1β were stained with polyclonal antibodies. A double immunofluorescence staining was performed to identify endometrial cells. Macrophage and lymphocyte rates were defined as the percentage of stained cells by field. Double staining was compared among macrophages, T lymphocytes, and anti-IL antibodies in each group.Results:The macrophage rate was high for women bearing an intrauterine device, intermediate for sterile patients, and low for fertile women (P = 0.03). There was a lack of double staining between activated T lymphocytes and anti–IL-6 antibody in tubal sterility and endometriosis. Endometrial macrophages were stained with anti-IL antibodies for all groups.Conclusions:Endometrial macrophages seem to be an interesting parameter for evaluating endometrial inflammation. In tubal infertility and endometriosis, the lack of expression of IL-6 in T lymphocytes could participate in impaired embryo implantation.

Successful in vitro fertilization–surrogate pregnancy in a patient with ovarian transposition who had undergone chemotherapy and pelvic irradiation

OBJECTIVE To present a case of IVF-surrogate pregnancy in a patient with ovarian transposition who had undergone chemotherapy and total pelvic irradiation. DESIGN Case report. SETTING Teaching hospital. PATIENT(S) A 29-year-old woman who had undergone Wertheims hysterectomy for a bulky carcinoma of the uterine cervix. INTERVENTION(S) Ovarian transposition before chemotherapy and total pelvic irradiation. Standard IVF treatment, transabdominal oocyte retrieval, and transfer to the surrogate mother. MAIN OUTCOME MEASURE(S) Results of the IVF cycle. RESULT(S) A twin pregnancy at the first cycle and two live newborns. CONCLUSION(S) This is the first reported case of ovulation induction and oocyte retrieval performed on a transposed ovary.