Live birth in a woman without ovaries after autograft of frozen-thawed ovarian tissue combined with growth factors.

Currently, cryopreservation of oocytes, embryos and ovarian tissue is considered the basis of fertility preservation programs for women with cancer and other diseases who are rendered sterile by gonadotoxic drugs or radiation.Numerous studies have confirmed that autograft of frozen-thawed ovarian tissue can restore ovarian function and fertility. A total of twenty-two live births have been reported but we still have to consider this technique as experimental. The main problem is that the implant undergoes ischemia until neoangiogenesis is restored, resulting in significant follicular loss.At the moment, there are numerous publications in different medical fields that publish successful experiences with plasma rich in platelets (PRP) in different clinical situations promoting angiogenesis. Thus, we considered the possibility of using it in the field of ovarian autologous transplantation in order to improve the vascularization of the implant and its quality. For this, both thawed ovarian tissue as practiced pockets on the rear side of the broad ligament which have been placed, have been impregnated with PRP. We can say that the implant treated in this way has had a rapid and successful response.We report a special interesting case because this is the first time that this technique is performed successfully in a woman without ovaries combined with growth factors to promote neoangiogenesis. Obviously, the results of the hormonal response come exclusively from the implanted tissue in these special conditions.

Use of letrozole in assisted reproduction: a systematic review and meta-analysis.

BACKGROUND: Letrozole is the third-generation aromatase inhibitor (AI) most widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen production; the consequent hypoestrogenic state increases GnRH release and pituitary follicle-stimulating hormone (FSH) synthesis. METHODS: A systematic search of the literature was performed for both prospective and retrospective studies. Meta-analyses of randomized clinical trials (RCTs) were performed for three comparisons: letrozole versus clomiphene citrate (CC), letrozole + FSH versus FSH in intrauterine insemination (IUI) and letrozole + FSH versus FSH in IVF. In the absence of RCTs, non-randomized studies were pooled. RESULTS: Nine studies were included in the meta-analysis. Four RCTs compared the overall effect of letrozole with CC in patients with polycystic ovary syndrome. The pooled result was not significant for ovulatory cycles (OR = 1.17; 95% CI 0.66-2.09), or for pregnancy rate per cycle (OR = 1.47; 95% CI 0.73-2.96) or for pregnancy rate per patient (OR = 1.37; 95% CI 0.70-2.71). In three retrospective studies which compared L + FSH with FSH in ovarian stimulation for IUI, the pooled OR was 1.15 (95% CI 0.78-1.71). A final meta-analysis included one RCT and one cohort study that compared letrozole + gonadotrophin versus gonadotrophin alone: the pooled pregnancy rate per patient was not significantly different (OR = 1.40; 95% CI 0.67-2.91). CONCLUSIONS: Letrozole is as effective as other methods of ovulation induction. Further randomized-controlled studies are warranted to define more clearly the efficacy and safety of letrozole in human reproduction.

Polycystic ovaries in nonobese adolescents and young women with ovarian androgen excess: relation to prenatal growth.

OBJECTIVE: Reduced growth before birth is known to associate with a smaller ovarian volume in adolescents and women without androgen excess. We studied whether prenatal growth relates also to ovarian size and polycystic ovary (PCO) morphology in nonobese adolescents and young women with ovarian androgen excess. DESIGN: A cross-sectional analysis of standardized case notes over a 2-yr period was performed. PATIENTS: Nonobese adolescents and young women (age approximately 17 yr; n = 86) seen for ovarian androgen excess, as confirmed by 17-hydroxy-progesterone hyperresponse to a GnRH agonist, were included in the study. MEASUREMENTS: Endocrine-metabolic assessment in fasting state, together with a vaginal ultrasound scan to verify the presence or absence of PCO was performed. Birth weight and gestational age were derived from medical records. RESULTS: PCO prevalence by ultrasound was 38%. Absence of PCO was associated with a shift (P < 0.0005) of the birth weight distribution toward lower values. Patients with a birth weight less than 3.0 kg were 6-fold more likely to have no PCO than to have PCO. Birth weight was across a wide range (1.5-4.0 kg) associated with ovarian volume in hyperandrogenic patients with noncystic ovaries (r = 0.60; P < 0.00001) and was, in a multiple regression analysis, the prime variable linked to ovarian volume (beta = 0.57; P < 0.00001), explaining 32% of its variance. CONCLUSIONS: The ovarian size and the development of a PCO morphology in nonobese adolescents and young women with ovarian androgen excess relate to prenatal growth. These findings indicate that there are two subgroups of nonobese patients with ovarian androgen excess: one with a normal birth weight distribution and with PCO, and one with lower birth weights and without PCO.

Hormonal environment in the induction of breast cancer in castrated rats using dimethylbenzanthracene: influence of the presence or absence of ovarian activity and of treatment with estradiol, tibolone, and raloxifene.

OBJECTIVE: The influence of hormone therapy on the induction or the promotion of breast cancer has yet to be determined. Recent studies establish a cause-effect relation between hormones and cancer, although epidemiological data and studies of tumor behavior give rise to doubts. The aim of the study was to observe and evaluate the influence of different hormonal environments on the induction of breast cancer in a well-established experimental model. DESIGN: In this experimental animal study, breast cancer was induced by using a single intragastric dose of 20 mg of dimethylbenzanthracene in prepubertal Sprague-Dawley rats randomized into five groups: group 1 (control); group 2 (castrated prepubertal animals); and groups 3, 4, and 5 (castration of prepubertal animals followed by hormonal treatment starting at puberty [11 weeks] with tibolone, raloxifene, and estradiol, respectively). Follicle-stimulating hormone and estradiol levels were measured at 6, 11, 16, and 31 weeks. RESULTS: Absence of ovarian activity was observed in groups 2, 3, 4, and 5, as well as the expected variations in hormone levels in all groups. Breast cancers were obtained in 100% of the animals in the control group, with an average of four (two to seven) tumors per animal in this group. Only one cancer appeared in groups 2, 3, and 4, and none appeared in group 5. CONCLUSIONS: In this experimental model and using the hormone treatments chosen, neither the treatments nor the absence of ovarian activity induced breast cancer.

Evolution of Spanish scientific production in international obstetrics and gynecology journals during the period 1986-2002.

OBJECTIVE: The present bibliometric study analyzes Spanish scientific work published in the field of obstetrics and gynecology in the most important journals during the period 1986-2002. STUDY DESIGN: The material studied (779 original documents) was selected in accordance with the science citation index (SCI) of 2001, obstetrics and gynecology section, using the EMBASE: Obstetrics and Gynecology database. We applied the customary rules of bibliometrics: Price's Law of increase in scientific literature, Bradford's Law of scattering of scientific literature and Lotka's Law of author productivity. Furthermore, we analyzed participation index (PaI), the collaboration index and the superior (%SUP). RESULTS: The material studied is closer to an exponential adjustment (r = 0.958) than to a linear adjustment (r = 0.856). The journal with the largest number of originals is Human Reproduction (Bradford's first area), with 217 articles and that with the highest PaI is Menopause (4.07). The total number of authors is 1829, who are responsible for 3938 authorships (2.79% of the authors have a productivity index (PI) > or = 1 and 70.09% have a PI = 0). The majority of the studies were carried out in hospitals (47.62%) and universities (23.36%). CONCLUSION: Spanish productivity in the field of obstetrics and gynecology increased considerably in the period 1986-2002.

Inhibin and follicular development in heterotopical ovary transplants without vascular pedicle in syngeneic Lewis rats.

OBJECTIVE: To evaluate the role of inhibin in elevated base levels of FSH and follicular hyperplasia in ovarian autotransplantation in rats. DESIGN: Experimental animal study. SETTING: Unit of Experimental Research at the Barcelona University School of Medicine. ANIMAL(S): Female syngeneic Lewis rats aged 16 weeks. INTERVENTION(S): The animals were randomized into two groups: group A, control group undergoing only laparotomy (n = 5) and group B, oophorectomized with SC autologous heterotopic transplant (n = 5). The animals were killed and their ovaries removed for histologic, morphometric, and immunohistochemical analysis at 28 days after surgery in both groups. MAIN OUTCOME MEASURE(S): Serum levels of E2 and FSH were determined on day 0 (the day of surgery or baseline) and days 4, 7, 14, 21, and 28. Morphometric analysis of ovarian structure for evaluation of antral follicles and their granulosa cell area and immunohistochemistry for inhibin staining were also done. RESULT(S): The endocrinological function recovered at 28 days, and the FSH levels for the transplant group were significantly higher than for the group with normoinsert ovary. Morphometric analysis showed that the mean granulosa cell area was greater in group B when compared with the control group. Immunohistochemistry revealed almost null inhibin staining of the stroma in transplanted ovarian tissue. CONCLUSION(S): Tissue damage brought on by ischemia in the transplant of nonvascularized ovaries may bring about an inhibin deficit in the ovarian stroma, which might explain the increased levels of FSH. These increased levels, in turn, would be responsible for the follicular hyperplasia seen in this tissue when it recovers its function.

Heterotopic ovarian transplantation without vascular pedicle in syngeneic Lewis rats: long-term evaluation of effects on ovarian structure and function.

OBJECTIVE: To assess the long-term efficacy of intraperitoneal (IP) and subcutaneous (SC) ovarian autotransplantation in rats. DESIGN: Experimental animal study. SETTING: Unit of Experimental Research, Barcelona University School of Medicine. ANIMAL(S): Female syngeneic Lewis rats aged 14 weeks. INTERVENTION(S): Group A, control group undergoing ovariectomy (n = 15); group B, undergoing ovariectomy and IP autologous heterotopic transplant (n = 15); and group C, ovariectomized with SC autologous heterotopic transplant (n = 15). In groups B and C, five animals were killed and their ovaries removed for morphometric analysis at 30 days after transplantation; five additional animals were killed at 180 days, and the remaining five animals were killed at 360 days. MAIN OUTCOME MEASURE(S): Ovarian morphometric analysis and serial measurement of E(2) and FSH serum levels. RESULT(S); The mean number of antral follicles in the control group A was significantly higher than that observed in the ovarian grafts collected and examined 30 days after grafting in rats from groups B and C, but the mean granulosa cell area was significantly higher in both transplantation groups than in controls because of ovarian follicular hyperplasia. Histological examination of ovaries removed at 6 and 12 months after grafting in groups B and C showed increasing degrees of fibrosis, loss of primordial follicles, and the presence of epithelial cysts. In groups B and C, from day 30 after surgery onward, serum E(2) was significantly higher and FSH significantly lower, respectively, than in group A. E(2) and FSH patterns in groups B and C were similar throughout the study period. CONCLUSION(S): Heterotopic ovarian transplantation without vascular pedicle in rats is characterized by follicular hyperplasia endocrinologically functional, followed by progressive loss of follicles in heterotopic ovarian autografts.