The predictive value of ovarian reserve tests for spontaneous pregnancy in subfertile ovulatory women.

BACKGROUND: The predictive value of ovarian reserve tests (ORTs) for spontaneous pregnancy is unclear. Our study aimed to determine whether ORTs have added value to previously identified prognostic factors for spontaneous pregnancy in subfertile ovulatory couples. METHODS: A prospective cohort study was performed on 474 subfertile ovulatory couples in two hospitals in Groningen, The Netherlands. The ORTs performed were: antral follicle count (AFC), follicle-stimulating hormone (FSH), inhibin B (basal levels and after stimulation with clomiphene citrate) and the clomiphene citrate challenge test. For each couple, the probability of spontaneous pregnancy was retrospectively calculated using the validated Hunault prediction model which includes the main known prognostic factors for spontaneous pregnancy. Outcome measure was time to spontaneous pregnancy resulting in a live birth. RESULTS: When added to the Hunault model, only basal FSH and AFC significantly improved the prediction of spontaneous pregnancy (P-values of 0.05 and 0.04). Absolute changes in predicted probabilities after adding basal FSH or AFC were small: the predicted probability of spontaneous pregnancy shifted >or=10% in only 3.8% and 7.9% of the couples, respectively. CONCLUSIONS: Although basal FSH and AFC significantly improved the validated prediction model for spontaneous pregnancy, the clinical relevance of this finding is limited. We recommend that none of the ORTs studied should be used routinely in the subfertility evaluation of ovulatory couples to predict spontaneous pregnancy chances.

The number of small antral follicles (2-6 mm) determines the outcome of endocrine ovarian reserve tests in a subfertile population.

BACKGROUND: Ovarian reserve is related to age and can be estimated by ovarian reserve tests (ORTs), such as antral follicle count (AFC) and various endocrine parameters. The endocrine function of a follicle is related to its size. The aim of this study is to evaluate which sizes of antral follicles are most closely correlated with age and the outcome of endocrine ORTs. METHODS: In total 474 subfertile, ovulatory patients, recruited from two fertility centers in The Netherlands, participated in this prospective cohort study. The following ORTs were performed: AFC (follicles from 2 to 10 mm), basal FSH, basal inhibin B (bInhB), clomiphene citrate challenge test and inhibin B after stimulation with clomiphene citrate. RESULTS: The number of small follicles (2-6 mm) declined with age; the number of larger follicles (7-10 mm) remained constant. Independent of age, the number of small follicles was significantly related to all ORTs (P<0.001, except bInhB P=0.005). The number of larger follicles was only significantly related to bInhB (P=0.009). CONCLUSIONS: The number of small antral follicles (2-6 mm) is significantly related to age and also, independent of age, to all endocrine ORTs tested, suggesting the number of small antral follicles represents the functional ovarian reserve.

Women's opinion on the use and offer of ovarian reserve testing: a first step towards a wide ranged social discussion.

OBJECTIVE: To determine the opinion among three groups of women (sub-fertile women, fertile women and female medical students), concerning the use of ovarian reserve tests to determine the chance of an assisted reproductive techniques' (ART) induced pregnancy or a spontaneous pregnancy. DESIGN: Prospective study using questionnaires in three groups of women: patients visiting the out patient infertility clinic at the Academic Medical Centre Groningen, women who had delivered at least two children and female medical students. RESULTS: The response rate varied from 63% (female medical students) to 56% (fertile women with children) and 48% (sub-fertile women). The greater part of women of all three groups found it was up to the women themselves to decide whether or not to start fertility treatment, even though the ovarian reserve test indicated little chance of success. 71% of the sub-fertile women stated that any chance justified fertility treatment. None of the three groups of women were very enthusiastic about the use of these tests for family planning. CONCLUSIONS: Based on results of ovarian reserve tests women could decide not to partake of a - generally demanding - fertility treatment. The outcome of the study, however, does not support this: even low chances of success are found acceptable. The ability to determine the individual ovarian reserve makes this test also a suitable device for family planning. The discussion whether these new possibilities will be useful for reproductive science will greatly depend on women's attitude towards this issue.

Ovarian reserve testing and the use of prognostic models in patients with subfertility.

The decline in fecundity with female age is a well-known phenomenon for clinicians dealing with subfertility patients. Diminishing ovarian reserve seems to be the reason for declining fecundity. Since age is only a rough estimate of ovarian reserve, many tests have been developed to predict ovarian reserve more precisely. This review focuses on these ovarian reserve tests and their clinical role in predicting response to ovarian stimulation and pregnancy chances. According to our analysis, the clomiphene citrate challenge test has the strongest correlation in predicting ovarian reserve, and is the only test that is validated in the general infertility population. The antral follicle count by ultrasound is promising and may offer clinical use. It is not known whether a combination of tests can provide more accurate information of ovarian reserve. It is not yet clear to which extent the results of ovarian reserve tests can be incorporated into the available prognostic models. There is a need for prospective cohort studies that focus on prognostic factors among which are the results of ovarian reserve tests. Only then can the qualitative and quantitative relevance of ovarian reserve testing in the context of the prognosis for couples with subfertility be established.

Long-term effects of chemotherapy in patients with testicular cancer.

PURPOSE: Combination chemotherapy regimens that include cisplatin (CDDP) and bleomycin (BLE) result in the cure of the majority of patients with malignant germ cell tumors of the testis. We investigated the long-term damage of such chemotherapy to renal, pulmonary, and hearing function. PATIENTS AND METHODS: Forty-three patients with disseminated testicular carcinoma were studied 1.5 to 9.3 years (median, 4.1 years) after completion of chemotherapy. All 43 patients received CDDP; of these, 39 also received BLE, 27 vinblastine (VLB), and 27 etoposide (VP-16). Mean cumulative doses of individual cytotoxic drugs administered were CDDP 483 mg/m2 (range, 189 to 1,173 mg/m2), BLE 160 mg/m2 (range, 81 to 311 mg/m2), VLB 31 mg/m2 (range, 19 to 158 mg/m2), and VP-16 667 mg/m2 (range, 242 to 1,455 mg/m2). RESULTS: In the majority of cases, values of renal, pulmonary, and hearing function were within the normal range before treatment. An initial decrease in renal, pulmonary, and hearing function was observed, with recovery of pulmonary function at late follow-up. On average, a decrease of 15% in creatinine clearance rates was observed at late follow-up. Long-term effect on audiometric function was considerable, but frequencies affected were outside the range of conversational speech. With multivariate analysis, no overall relation between the cumulative doses of the individual drugs and the loss in organ function was found; the cumulative doses of CDDP and BLE only contributed approximately 30% to the loss in renal function and vital capacity, respectively. CONCLUSION: Chemotherapy-induced pulmonary toxicity is reversible, whereas nephrotoxicity and ototoxicity are not. However, the long-term effects of chemotherapy in testicular cancer patients were minor and not invalidating.

Antiprogestagenic inhibition of uterine prostaglandin inactivation: a permissive mechanism for uterine stimulation.

The use of antiprogestins as abortifacients is more effective when antiprogestin priming is followed by the administration of a small dose of synthetic prostaglandin. This increased myometrial sensitivity towards PG has not been explained and experiments in the guinea-pig where no myometrial activity is observed after 48 h of antiprogestin administration together with measurements of PG metabolites in uterine vein blood have given rise to the suggestion that prostaglandin synthesis is inhibited by antiprogestins. We have treated groups of 50 day pregnant guinea-pigs with 10 mg RU486 or vehicle alone and examined the ability of homogenised uterine tissues (myometrium/decidua, cervix, chorion and amnion) to metabolize PGE when given a large excess of substrate and sufficient cofactors. In addition we have examined the ability of these homogenates to synthesis PG. Antiprogestin treatment in vivo resulted in a 9-fold reduction in metabolic activity in chorion (P less than 0.02) and a 4-fold reduction in myometrium/decidua (P less than 0.02). Reduction in activity seen in amnion and cervix was not significant. The maximum metabolism was seen in the chorion and minimal metabolism in the amnion. Maximum PG production was seen in the amnion and minimum in the chorion. These results show that the effect of antiprogestin in reducing prostaglandin catabolism would reduce the threshold above which PG production would cause contractions which would in turn stimulate PG production. Thus an explanation is provided of how low doses of exogenous PGs or transient synthesis of endogenous PG within an antiprogestin treated uterus can led to a self sustaining cycle of stimulation which will lead to abortion.