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Atretic demise rather than ovulation is the ultimate fate of the vast majority of ovarian follicles in mammals, affecting 70-99.9% of the follicles in various species. Recent studies have established that atretic degeneration of follicles is an apoptotic process, heralded by endonuclease degradation of DNA at internucleosomal sites, which generates DNA fragments in size multiples of 185-200 bp that are seen as distinct ladder bands after agarose gel electrophoresis. Using the well-characterized model of inducing atresia of preovulatory follicles in vivo by hypophysectomy and analyzing DNA fragmentation by autoradiography of size-fractionated DNA labeled at the 3' ends by [12P] dideoxy-ATP, we have examined the timing of atretic changes. DNA degradation was related to morphological signs of atresia, ovulability, and changes in follicular steroidogenesis. Rats were hypophysectomized on the morning of the day of proestrus, after which largest follicles were collected at various times. DNA fragmentation was analyzed in groups of five follicles. The increase in DNA fragments of low molecular weight up to 4 h after hypophysectomy was negligible (101 +/- 10%; 0 h time = 100%) but progressed 8, 12, 24, 48, and 72 h after hypophysectomy (143 +/- 20%, 168 +/- 27%, 235 +/- 29%, 3299 +/- 1075%, and 2249 +/- 805%, respectively; p < 0.03, n = 5). At 48 and 72 h, the extent of DNA degradation was higher than that observed in follicles cultured in a serum-free medium for 24 h. Likewise, staining of DNA by 4',6-diamido-2-phenylindole hydrochloride revealed apoptotic nuclei at 8 h after hypophysectomy (p < 0.01), and the percentage of such nuclei progressively increased afterwards. Thus, the increase in DNA fragmentation appeared concomitantly with atretic changes observed in previous studies (a decrease in ovulability at 6 h, and a spontaneous increase in progesterone accumulation and decrease in androgen and estrogen in follicles explanted 6 h after hypophysectomy) and preceded atresia detectable by morphological changes at 24 h. Detection of internucleosomal DNA degradation in preovulatory follicles early in the atretic cascade underscores the central role of apoptosis in ovarian follicle atresia.

In a retrospective study of 813 oocyte retrieval-embryo transfer cycles in women with normal follicle stimulating hormone and luteinizing hormone concentrations, we sought to investigate the relationship between the amount of human menopausal gonadotrophin (HMG) used for ovarian stimulation and treatment outcome. Patients were divided into three groups: group A patients (495 cycles) required < 40 ampoules of HMG and had a predicted probability for pregnancy of 25% per embryo transfer; group B patients (165 cycles) required 41-77 ampoules per cycle, with a predicted probability rate for pregnancy of 5-25% per embryo transfer; and group C patients (153 cycles) required > 77 ampoules of HMG and the predicted probability for pregnancy was < 5% per embryo transfer. Groups C and A differed significantly (P < 0.005). The mean oestradiol concentration on the day of HCG administration in group C was 6412 pmol/l, and the mean number of eggs retrieved was seven. The highest success rates were found when up to 2.5 ampoules of HMG were required for each egg or 4.4 ampoules for each embryo. The lowest rates were obtained when > 4.8 ampoules of HMG were necessary for each oocyte or > 9.6 ampoules for each embryo (P < 0.005). We identified a group of infertile patients who required excessive amounts of HMG to achieve a fair degree of steroidogenesis, number of eggs and number of embryos but who had very low pregnancy rates. Although all other relevant parameters were normal, this may highlight the beginning of ovarian-gamete insufficiency before the basic hormonal status is affected. In cases of repeated failure, oocyte donation should be considered.

Chronic Q fever has been associated with endocarditis, granulomatous hepatitis, and osteomyelitis but only rarely with pregnancy. The apparent predilection of Coxiella burnetii, the organism causing Q fever, for the human placenta suggests that chronic Q fever of pregnancy is due to placentitis. We describe a patient with chronic, clinically apparent Q fever in pregnancy and a successful outcome. The diagnosis was made both by serology and by isolation of C. burnetii from the patient's serum and placenta. Therapy with erythromycin and rifampin contributed to the delivery of a healthy baby. The mother's infection was clinically cured by subsequent therapy with doxycycline and rifampin.

Repeated attempts with oral oestrogens and injectable progesterone failed to induce secretory endometrium in a woman with 17-alpha-hydroxylase deficiency. The insertion of s.c. 17-beta-oestradiol implants dramatically improved the endometrial response and enabled the establishment of endometrial maturation. A viable pregnancy was achieved after the uterine transfer of in-vitro fertilized donated eggs.

Pre-menopausal tamoxifen treatment causes hyperoestrogen production and ovarian cyst formation. Two pre-menopausal breast cancer patients who were treated with tamoxifen developed both permanent supraphysiological oestrogen concentration and ovarian cysts. Serum oestrogen decreased to post-menopausal concentrations and ovarian cysts completely resolved during and following simultaneous treatment with tamoxifen and gonadotrophin-releasing hormone agonist (GnRHa). In pre-menopausal breast cancer patients, GnRHa may prevent possible side-effects of tamoxifen, such as ovarian cysts and supraphysiological oestrogen production.

A case is presented of a twin gestation comprising a grossly normal fetus and placenta coexisting with a separate hydatidiform mole which ended in an abortion. Both developed following ovulation induction with human menopausal gonadotrophin and human chorionic gonadotrophin. The literature is reviewed and clinical aspects of this rare entity are discussed.