Apoptosis is a type of physiologic cell death that occurs in many tissues and be regulated by peptide growth factors. Recent studies indicate that apoptosis occurs in the ovary during follicular atresia in several animal species, including the rat, pig, chicken, baboon, and rabbit. The purpose of this study was to demonstrate, through in situ identification of apoptotic cells in intact ovarian sections, the sites in which apoptosis occurs in the rat ovary in different functional states. We evaluated the presence of apoptosis in three models: immature rats, eCG-treated rats and adult cycling rats. Paraffin ovarian sections were pretreated with proteinase K and then end-labeled with biotinylated deoxyuridine triphosphate (dUTP) by incubation with the enzyme terminal deoxynucleotidyl transferase (TDT). They were then stained through use of avidin-conjugated peroxidase with 3,3'-diaminobenzidine as the substrate. Healthy antral and preantral follicles had no staining. The nuclei of granulosa cells of preantral and antral atretic follicles were positively stained in all the animal groups. Scattered theca cells were also stained. Stromal cells were consistently negative. Positive controls were sections pretreated with DNase I; these displayed intense staining of all nuclei. Negative controls, in which either terminal TDT or its biotinylated substrate was omitted, were appropriately negative. This study represents a systematic analysis of apoptosis in the rat ovary at different functional stages and supports the hypothesis that apoptosis is involved in the process of follicular atresia.

Angiotensin II (Ang II) is present in high concentrations in preovulatory follicular fluid, and ovarian follicular cells have specific Ang II receptors. To investigate the possible direct involvement of Ang II in ovulation the specific receptor antagonist of Ang II, saralasin, was administered by intraperitoneal injection to immature rats in which follide development and ovulation had been induced with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG), respectively. Saralasin halved the number of oocytes found in the fallopian tubes 17 to 20 hours after administration of hCG. The antiovulatory effect was observed when saralasin was given 1 hour before hCG or 1 or 3 hours after hCG but not when given 5 hours after hCG. Simultaneous administration of Ang II reversed the saralasin blockage of ovulation. These results indicate a direct, obligate role for Ang II in ovulation and raise the possibility of contraceptive and profertility applications for agonists or antagonists of the renin-angiotensin system that are aimed at the ovulatory process.

BACKGROUNDDespite many advances in assisted reproductive techniques (ART), little is known about preferences for technological developments of women undergoing fertility treatments. The aims of this study were to investigate the preferences of infertile women undergoing ART for controlled ovarian stimulation (COS) treatments; to determine the utility values ascribed to different attributes of COS treatments; and to estimate women's willingness to pay (WTP) for COS.METHODSA representative sample of ambulatory patients ready to receive, or receiving, COS therapies for infertility were recruited from seven specialized private centres in six autonomous communities in Spain. Descriptive, inferential and conjoint analyses (CA) were used to elicit preferences and WTP. Attributes and levels of COS treatments were identified by literature review and two focus groups with experts and patients. WTP valuations were derived by a combination of double-bounded (closed-ended) and open questions and contingent ranking methods.RESULTSIn total, 160 patients [mean (standard deviation; SD) age: 35.8 (4.2) years] were interviewed. Over half of the participants (55.0%) had a high level of education (university degree), most (78.8%) were married and half (50.0%) had an estimated net income of >€1502 per month and had paid a mean (SD) €1194.17 (€778.29) for their most recent hormonal treatment. The most frequent causes of infertility were related to sperm abnormalities (50.3%). In 30.6% of cases, there were two causes of infertility. The maximum WTP for COS treatment was €800 (median) per cycle; 35.5% were willing to pay an additional €101–€300 for a 1–2% effectiveness gain in the treatment. Utility values (CA) showed that effectiveness was the most valued attribute (39.82), followed by costs (18.74), safety (17.75) and information sharing with physicians (14.93).CONCLUSIONSWTP for COS therapies exceeds current cost. Additional WTP exists for 1–2% effectiveness improvement. Effectiveness and costs were the most important determinants of preferences, followed by safety and information sharing with physicians.

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