Ovulation before or after intrauterine insemination does not affect live birth rates: a retrospective cohort study of 6701 cycles.

RESEARCH QUESTION: Should intrauterine insemination be carried out before or after follicle rupture, and is there a difference in sex ratio, according to follicle rupture at the time of insemination? DESIGN: In this retrospective cohort study conducted at the Fertility Clinic, Odense University Hospital, Denmark, data from 6701 homologous insemination cycles were analysed. Follicle rupture was determined by transvaginal ultrasonography at the time of insemination. The pregnancy rate, clinical pregnancy rate (CPR) and live birth rate (LBR) were recorded. RESULTS: In 2831 cycles (42.2%), follicle rupture had occurred at the time of insemination, whereas, in 3870 cycles (57.8%), no follicle rupture had occurred at the time of insemination. Overall, 1186 (17.7%) cycles resulted in a positive pregnancy test and no significant differences were found in pregnancy rate between rupture and no rupture of follicle (17.8% versus 17.7%, P = 0.90). Follicle rupture before or after insemination did not affect CPR (14.8% versus 15.0%, P = 0.86) or LBR (11.9% versus 12.2%, P = 0.75) per cycle. Moreover, the sex ratio of children born did not depend on follicle rupture (P = 0.20). After logistic regression with cluster and adjusting for baseline characteristics, no significant differences between groups were observed. CONCLUSION: Ovulation at the time of insemination is not associated with pregnancy rate, CPR, LBR or gender.

Cryopreservation of ovarian tissue for fertility preservation: no evidence of malignant cell contamination in ovarian tissue from patients with breast cancer.

Cryopreserved ovarian cortical biopsies from 51 patients with breast cancer were examined by histologic and immunohistochemical analysis and showed no sign of metastases. Autotransplantation of ovarian cortex to patients with low-stage breast cancer disease appears safe, but confirmatory studies are required, including xenotransplantation studies.

Cryopreservation of ovarian tissue for a decade in Denmark: a view of the technique.

This paper presents the Danish 10-year experience (1999-2009) with cryopreservation (n=386) and autotransplantation of ovarian tissue (n=18). Before applying the technique to humans, the method was thoroughly tested and validated. The cryoprotectant solution was chosen after histological evaluation of mouse and human ovarian tissue after freezing with four different combinations of cryoprotectants. Viability was confirmed by transplantation of frozen-thawed human ovarian tissue (n=49) to oophorectomized Nude mice. Viability after transport of fresh tissue 4-5h prior to freezing had previously been validated. Overnight transport of fresh ovarian tissue prior to cryopreservation was evaluated when human ovarian tissue was kept on ice for 20h and then cryopreserved. The thawed ovarian tissue was transplanted to an oophorectomized Nude mouse and histology confirmed viability. In Denmark 12 women have received a total of 18 autotransplantations of ovarian tissue. All women resumed ovarian function and three healthy babies were born to two women. In both women, the tissue was transported on ice for 4-5h prior to cryopreservation. Ovarian tissue cryopreservation is an important method for fertility preservation; however, before applying the method clinically, each laboratory should perform thorough validation of their technique.

True ovarian volume is underestimated by two-dimensional transvaginal ultrasound measurement.

OBJECTIVE: To investigate a possible difference between true ovarian volume and ovarian volume estimated with two-dimensional (2D) transvaginal ultrasound. DESIGN: Prospective clinical and laboratory study. SETTING: University hospital research laboratory. PATIENT(S): Premenopausal girls and women from three Danish national fertility centers (A: n = 42; B: n = 6; C: n = 18), who had one entire ovary removed for cryopreservation of ovarian cortex. INTERVENTION(S): Transvaginal 2D ultrasound measurement of ovarian volume before oophorectomy. True ovarian volume was obtained by weighing the ovary. MAIN OUTCOME MEASURE(S): Ovarian volume estimated by weight and ultrasound. RESULT(S): Ovarian tissue density was 1.00 g/mL. Mean ovarian volume by ultrasound vs. weight in the three groups was as follows: A: 6.3 mL vs. 7.8 mL; B: 5.4 mL vs. 6.8 mL; and C: 2.8 mL vs. 6.1 ml. Ovarian volume obtained by ultrasound was at least 27% smaller than the true ovarian volume. CONCLUSION(S): Ovarian volume was severely underestimated by transvaginal 2D ultrasound measurement.

Ovarian function after removal of an entire ovary for cryopreservation of pieces of cortex prior to gonadotoxic treatment: a follow-up study.

BACKGROUND: Ovarian function was studied in Danish patients who had ovarian tissue cryopreserved, and the patients' experiences with the procedure were investigated. METHODS: There were 92 women who had an entire ovary removed for cryopreservation 18-75 months earlier. Reasons included: breast cancer (n = 31; 34%), Hodgkin's lymphoma (n = 23; 25%), bone marrow transplantation (BMT) (n = 19; 21%) and others (n = 19; 21%). Patients completed a questionnaire, and transvaginal ultrasonic antral follicle count and serum analysis for follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) were performed in 73 women. RESULTS: In total, 11% of the BMT patients had normal ovarian function. Hodgkin's patients who only received ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) (n = 12) and 60% of the breast cancer patients showed little evidence of ovarian damage. Regular menstruation was shown to be a good indicator of ovarian function. The cryopreservation procedure rarely complicated cancer treatment (5%) and 84% felt comforted because they had potentially secured their fertility. CONCLUSIONS: Cryopreservation of ovarian tissue should be considered in young female patients with Hodgkin's lymphoma receiving more aggressive treatment than ABVD and in patients scheduled for BMT. The recommendation for breast cancer patient should be individualized. The cryopreservation process did not delay cancer treatment.

Impact of follicular-fluid meiosis-activating sterol in an albumin-based formulation on the incidence of human pre-embryos with chromosome abnormalities.

OBJECTIVE: To evaluate the effect of adding follicular-fluid meiosis-activating sterol (FF-MAS) in a novel 0.2% recombinant human albumin-based formulation to cumulus-enclosed oocytes on chromosomal status and development of pre-embryos. DESIGN: Multicenter, prospective, randomized, open (double-blind for vehicle and FF-MAS groups), four parallel groups, controlled trial. SETTING: Four public IVF clinics in Denmark. PATIENT(S): Two hundred eighteen women undergoing IVF donated 483 oocytes. INTERVENTION(S): Follicle-stimulating hormone/hCG-primed cumulus-enclosed oocytes randomized to 4 hours of exposure to medium with 1 or 10 micromol/L of FF-MAS dissolved in 0.2% recombinant human albumin, medium with 0.2% recombinant human albumin (vehicle control), or medium alone (control) before insemination. MAIN OUTCOME MEASURE(S): Primary endpoint: incidence of human pre-embryos with chromosomal abnormalities. Secondary endpoint: fertilization rate, cleavage rate, and pre-embryo quality assessed after 68 hours of culture. RESULT(S): At pre-embryo level, the overall abnormality rates in the control, vehicle control, and 1- and 10-micromol/L FF-MAS groups were 53%, 39%, 42%, 53%, respectively, and at blastomere level 49%, 44%, 44%, and 48%, respectively. After 20 and 26 hours, the fertilization rates were between 67% and 71% in all groups. No differences in the cleavage rates were observed. CONCLUSION(S): The concentrations of FF-MAS in a novel 0.2% recombinant human albumin-based formulation of FF-MAS did not increase the risk of chromosomal abnormalities in pre-embryos or blastomeres. No statistically significant differences in fertilization rate, cleavage rate, or number of good quality pre-embryos were found among the four groups.

Prevalence of endocrine diseases and abnormal glucose tolerance tests in 340 Caucasian premenopausal women with hirsutism as the referral diagnosis.

OBJECTIVE: To perform an audit on the examination of hirsute patients and to establish a rational routine examination program in an outpatient endocrine clinic. DESIGN: Systematic, retrospective audit. SETTING: Academic tertiary-care medical center. PATIENT(S): Three hundred forty women with hirsutism as the referral diagnosis. INTERVENTION(S): Hormone analyses and ACTH tests during cycle days 2-8, 2 hours of oral glucose tolerance test (OGTT), and vaginal ultrasound. MAIN OUTCOME MEASURE(S): End diagnosis, fasting, 30-, 60-, and 120-minute oral glucose-stimulated levels of insulin and capillary blood glucose. RESULT(S): Two hundred one patients were diagnosed as having idiopathic hirsutism (IH) and 134 as having polycystic ovary syndrome (PCOS). End diagnosis: prolactinoma: n = 1, Cushing's syndrome: n = 1, androgen-producing ovarian tumor: n = 1, late-onset 21-hydroxylase defects: n = 2. During OGTT, 4.9% (13 of 263) had previously undiagnosed diabetes; no significant difference in diabetes prevalence was found between idiopathic hirsutism and PCOS. For 50.8%, fasting insulin values were in the upper quartile for a reference population. CONCLUSION(S): Initial evaluation of hirsute patients with irregular menses should include serum (s)-17alpha-hydroxyprogesterone, s-prolactin, s-Testosterone (T), and s-sex hormone-binding globulin. Further evaluation is needed in patients with markedly elevated s-T or with clinical Cushing's syndrome. Hirsute patients have a high risk of diabetes, although this could be due to the high number of overweight patients among this population.