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Objective: To evaluate the effect of premature P administration on artificially prepared endometrium in women with ovarian failure., Design: To mimic premature luteinization, patients with ovarian failure were treated with continuous estrogen and episodic P during the follicular phase of artificial cycles., Setting: In vitro fertilization unit at a university hospital., Patients: The study group included 16 patients with ovarian failure who were randomly divided into two groups. Group A (8 patients) was treated by episodic P administration during the artificial follicular phase on days 2 and 7 (12.5 mg of P in oil IM), and in group B (8 patients), P (6.25 mg) was added on days 3, 4, and 5. Another 16 patients (group C), age matched to the study group, were arbitrarily allocated to serve as controls and had standard preparatory cycles without P supplementation in the follicular phase. Serum E2 and P levels and endometrial biopsies were taken on days 14 and 26., Results: Serum E2 levels were comparable between the study group (group A+B) and controls on both days 14 and 26. Although serum P levels did not differ between the groups on day 26, it was higher in the follicular phase of the study group than in the controls (1.9 +/- 4.0 and 0.2 +/- 0.1 ng/mL, respectively). In the study group, 8 of 16 patients demonstrated early secretory changes in the late follicular phase biopsies, and 9 of 16 women developed stromal-glandular discrepancy in the late luteal phase. This differed significantly from the controls in which only one late luteal biopsy was out of phase., Conclusions: Episodic surges of P during the follicular phase may result in impaired endometrial development that cannot be corrected by P supplementation during the luteal phase. This unique model provides evidence for the potential detrimental effect of premature P secretion in the follicular phase on endometrial function.

Objective: To examine whether luteal E2 is obligatory for obtaining an adequately developed endometrium., Design: Survey of women with premature ovarian failure (POF) in a prospective, controlled, randomized study., Setting: In vitro fertilization unit in a tertiary care university medical center., Patients: Fourteen amenorrheic women with POF, candidates for oocyte donation, were divided into two distinct groups with seven women in each subgroup., Interventions: Endometrial priming with a fixed dose of oral micronized E2, 4 mg/d for 14 days, was similarly performed in the study and the control groups. Progesterone replacement during the luteal phase was also identical in the two groups and was accomplished by IM P in oil, 50 mg/d for another 14 days. Only the control group continued to have the same E2 regimen during the luteal phase., Main Outcome Measures and Results: Follicular phase mean E2 levels as well as luteal phase mean P levels were similar in both groups. However, luteal E2 levels differed significantly between the study and the control groups (21 +/- 5 and 692 +/- 199 pg/mL, respectively; conversion factor to SI units, 3.671). Nevertheless, histologic evaluation of endometrial biopsies on days 21 and 26 were similar for both groups. Endometrial gland dating, using light microscopy in the study and the control groups, on day 21, was 19.1 +/- 0.8 and 18.4 +/- 0.5, respectively, and on day 26, 25.4 +/- 0.8 and 25.9 +/- 0.5, respectively. Dating of the stroma in the two biopsies was also similar in both groups. Moreover, transmission electron microscopy performed in two patients of the study group showed typical characteristics of a secretory endometrium., Conclusions: Luteal E2 depletion in the human does not seem to adversely affect the morphological developmental capacity of the endometrium. Our results suggest that E2 secretion by the corpus luteum in the human does not appear to be obligatory for the development of a normal secretory endometrium. The actual receptivity of the endometrium after such preparation needs to be evaluated.

Objective: To review and appreciate the relevant data on assisted reproduction techniques and their potential complications., Data Resources: Major publications on assisted reproduction that include the information concerning complications associated with this practice., Results: Assisted reproduction is a common practice in modern reproductive medicine. Complications are associated with ovulation induction and the extracorporeal methods that are used for IVF-ET, GIFT, and zygote intrafallopian transfer (ZIFT). These complications are associated with laparoscopy, anesthesia, oocyte retrieval, and laboratory facilities. Pregnancies resulting from assisted reproduction are more complicated than spontaneous pregnancies. There are higher rates of ectopic, heterotopic, and multifetal pregnancies; abortions; and premature deliveries. Increased rates of perinatal mortality and morbidity result from prematurity, and higher rates of maternal diseases in pregnancy (preeclampsia, diabetes mellitus, bleeding, anemia) contribute to fetal intra-uterine growth restriction and maternal morbidity., Conclusions: Assisted reproduction practice should be well controlled in view of the potential for complications before and during pregnancies.

Objective: To examine the effect of GnRH analogue (GnRH-a) on the quality of frozen-thawed embryos and the pregnancy rate (PR) resulting from transfer., Design: A retrospective study of two groups of women undergoing transfers of frozen-thawed embryos. In group 1 ovulation induction with hMG was begun after hypophyseal desensitization with GnRH-a for 2 weeks. In group 2 ovulation was induced with hMG only. The freezing and thawing techniques were identical for both groups., Setting: In vitro fertilization unit at a university hospital., Patients: The study group (group 1) included 108 women who underwent 137 transfer cycles of frozen-thawed embryos, and the control group (group 2) included 44 women in 51 cycles of thawed ETs., Interventions: Ovum pick-up and ET techniques were the same for both groups. Methods of embryo freezing and thawing were identical, as were the morphological criteria for grading the embryos., Results: The morphology of embryos was similar in both groups, as was the number of embryos that had at least 50% intact blastomeres (83% +/- 23% and 78% +/- 30% for group 1 and group 2, respectively). The PR (16 of 137 [11.7%] and 6 of 51 [11.8%], respectively) as well as the abortion rate (30%) were similar for both groups., Conclusions: The use of GnRH-a does not affect the quality of embryos nor the pregnancy outcome. Because the yield of frozen embryos per ovum pick-up is higher in cycles stimulated by GnRH-a/hMG, the PR per pick-up cycle is thus anticipated to be higher.

Objective: To define a new category of unexplained infertility and its potential treatment., Design: Normal infertile couples underwent prospectively, cross-fertilization attempts in which the wife's oocytes were inseminated by the husband and donor semen. After recurrent failure of fertilization, cross insemination of donor oocytes was attempted with the husband sperm., Setting: In vitro fertilization unit at a teaching hospital., Patients: Three couples who were diagnosed as suffering of unexplained infertility and treated by in vitro fertilization (IVF)., Results: The female partner of these couples produced morphologically normal oocytes that were demonstrated to be functionally defective and failed to fertilize in vitro with both husband and donor sperm. Donated oocytes inseminated by the husband's sperm were fertilized in all patients, demonstrating the normal fertilizing ability of the husbands' semen. One patient conceived and delivered after an oocyte donation., Conclusions: Conclusive diagnosis of defective oocytes as a cause of infertility may be made only after IVF and oocyte donation.