A prospective evaluation of antral follicle function in women with 46,XX spontaneous primary ovarian insufficiency.

OBJECTIVE: To assess ovarian follicle function in women with 46,XX spontaneous primary ovarian insufficiency. DESIGN: Case-control with nested prospective cohort. SETTING: Clinical Research Center, National Institutes of Health. PATIENT(S): Women with primary ovarian insufficiency without estrogen replacement for 2 weeks (N = 97) and regularly menstruating control women (N = 42). INTERVENTION(S): Single injection of 300 IU hrFSH. MAIN OUTCOME MEASURE(S): Change in serum estradiol at 24 hours. RESULT(S): Antral follicles ≥3 mm were detected in 73% (69/95) of patients; both serum estradiol and progesterone levels correlated significantly with maximum follicle diameter in these women. Patients with a maximum follicle diameter ≥8 mm had significantly higher serum estradiol and progesterone levels and significantly lower FSH and LH levels compared with patients without such follicles. In controls estradiol levels increased significantly after FSH administration, but in patients this was not the case despite the presence of an antral follicle ≥8 mm. CONCLUSION(S): Most women with 46,XX spontaneous primary ovarian insufficiency have antral follicles detectable by ultrasound, suggesting that down-regulation of FSH receptors is not the predominant mechanism of follicle dysfunction. Evidence of progesterone secretion by antral follicles ≥8 mm in these patients is consistent with prior histologic evidence that follicle luteinization is the predominant mechanism of follicle dysfunction in this condition. Prospective controlled investigation designed to improve ovulatory function and fertility in these women is indicated.

Luteal supplementation in in vitro fertilization: more questions than answers.

OBJECTIVE: To update clinicians on different regimens of luteal phase supplementation in IVF-stimulated cycles and to identify areas that need further research in this subject. DESIGN: Literature review and critical analysis of published studies on luteal phase supplementation during the last 20 years. CONCLUSION(S): Luteal phase supplementation in IVF-stimulated cycles, both in gonadotropin releasing hormone agonist and antagonist protocols, is considered an essential requirement for optimal success rates. The date of initiation and discontinuation of supplemented hormones is not adequately studied in the literature. In most major controlled and randomized studies, there are no significant differences in success rates with progesterone supplementation alone, progesterone and estradiol, progesterone and human chorionic gonadotropin, and human chorionic gonadotropin alone. Success rates seem similar with intramuscular and vaginal progesterone administration with patient preference for the vaginal route. The optimal dose of progesterone has not been studied in a scientific way in the literature. The use of gonadotropin releasing hormone agonists for luteal phase supplementation in antagonist cycles appears to be promising, and is worthy of further investigation.

Optimal stimulation protocols for in vitro fertilization.

OBJECTIVE: To update clinicians on different gonadotropin regimens for ovarian stimulation for IVF including the use of urinary and recombinant gonadotropins, the value of added LH to FSH in the stimulation regimen, the use of GnRH agonists and antagonists, and the role of minimal stimulation protocols. DESIGN: Literature review and critical analysis of major articles during the last five years on ovarian stimulation for IVF. CONCLUSION(S): Urinary and recombinant gonadotropins, for ovarian stimulation for IVF, are probably equally safe and effective. The higher cost for recombinant products limits their worldwide use in IVF. Conflicting data exist regarding the benefit of adding LH to FSH in the stimulation regimens. The use of different GnRH-agonists, of varying potency, may account for different levels of LH suppression. Adding LH should be considered in severe situations of LH suppression such as with the use of potent GnRH-agonists or when GnRH-antagonists are introduced during the course of stimulation. GnRH-antagonists provide advantages to patients in terms of fewer injections, shorter stimulation days, and avoidance of adverse effects of agonists. The incidence of ovarian hyperstimulation syndrome is probably less with antagonists compared to agonists, with the option to use an agonist as a surrogate LH surge. Fixed and early start of the antagonist is probably more effective than an individualized and late start. The earlier reported lower pregnancy rates with antagonists compared to agonists is not fully understood and needs to be continually monitored. Minimal stimulation protocols using a combination of clomiphene citrate and gonadotropins are attractive and should be considered in some patients owing to lower costs and acceptable success rates. The optimal stimulation protocol for IVF should be an individualized regimen based on the patient's ovarian physiology and prior IVF experience, if any.