Clomiphene Citrate – Initiated Ovulation: The State of the Art. In: Wallach EE, Zacur HA (Eds). Reproductive Medicine and Surgery

Preimplantation loss of fertilized human ova: estimating the unobservable

Wilcox AJ et al., 2020 · Human reproduction (Oxford, England) · Free full text on PubMed Central

What proportion of fertilized human ova are lost before implantation? An estimated 40 to 50% of fertilized ova fail to implant. Preimplantation loss is not detectable with current technology. Published estimates of preimplantation loss range from 10 to 70%. STUDY DESIGN, SIZE, We combine data from epidemiologic, demographic, laboratory and in vitro fertilization studies to construct an empirical framework for the estimation of preimplantation loss. This framework is summarized in a user-friendly Excel file included in supplement. PARTICIPANTS/MATERIALS, SETTING, We draw from multiple sources to generate plausible estimates of fecundability, sterility, transient anovulation, intercourse patterns and the proportion of ova fertilized in the presence of sperm. We combine these estimates to generate a summary estimate of preimplantation loss. This estimate can be considered an average for couples in their prime reproductive years. MAIN Under a plausible range of assumptions, we estimate that 40 to 50% of fertilized ova fail to implant. LIMITATIONS, A crucial factor in estimating preimplantation loss is the probability that an ovum will be fertilized when exposed to sperm. Human data are available only from in vitro fertilization (IVF), which may not accurately represent events in vivo. We therefore assume a range of in vivo fertilization rates, from 64% (human IVF data) to 90% (mouse data). Our estimate of preimplantation loss takes into account the biological processes relevant to fertilization and loss. Using this empirical basis for estimation, we find support for the usual assumption that risk of loss is highest in the earliest days following fertilization. Furthermore, this framework can provide improved estimates as better reproductive data become available. To the extent that our estimates are accurate, more fertilized ova are apparently lost in vitro than in vivo, suggesting that further improvements in IVF success rates may be possible. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Intramural Program of the National Institute of Environmental Health Sciences, NIH. Professor Adashi serves as Co-Chair of the Safety Advisory Board of Ohana Biosciences, Inc. The other authors have no competing interests. N/A.

Oral clomiphene citrate and vaginal progesterone suppositories in the treatment of luteal phase dysfunction: a comparative study

Murray DL et al., 1989 · Fertil Steril

Oral clomiphene citrate (CC) and vaginal progesterone suppositories (PS) are common treatment modalities in luteal phase dysfunction (LPD). Little is known regarding the relative efficacy of these agents. To study the use of CC and PS in the management of LPD, a retrospective cohort study of patients presenting with infertility was undertaken. Sixty-five patients in whom LPD was diagnosed and corrected, as judged by endometrial biopsies, were studied; 35 were treated with PS and 30 with CC. Using Student's t-tests and chi-square analyses, the two treatment groups were demographically comparable. Using life-table analysis, no one therapeutic approach proved superior. Clomiphene citrate and PS are comparable treatment modalities in the setting of LPD given correction of endometrial lag.

Ovulation induction

Kennedy JL et al., 1987 · Obstet Gynecol Clin North Am

Methods to induce ovulation in anovulatory women have blossomed over the last three decades. The introduction of clomiphene citrate in 1960 allowed us for the first time to provoke follicle development in patients with normo or hyperestrogenic forms of anovulation. The development of human menopausal gonadotropins in the early 1960s gave us a much more powerful tool with which to influence ovulation in all forms of ovulatory disturbances. Elucidation of the pulsatile secretion of gonadotropin-releasing hormone together with its isolation and synthesis has allowed us to streamline our methods of inducing ovulation in hypothalamic amenorrheic patients by using endogenous control mechanisms to maximize both safety and effectiveness. However, there are problems yet to solve. Polycystic ovarian disease has long eluded our efforts to resolve its pathophysiology as well as to devise a consistently effective and safe means of treatment. Methods to restore ovulation in patients with polycystic ovarian disease refractory to clomiphene citrate is the quest of future investigations.

Fertility following bilateral ovarian wedge resection: a critical analysis of 90 consecutive cases of the polycystic ovary syndrome

Adashi EY et al., 1981 · Fertil Steril

Fertility following bilateral ovarian wedge resection (BOWR) was evaluated in a retrospective cohort study of 90 consecutive cases of the polycystic ovary syndrome. Post-BOWR follow-up was available for varying time spans of up to 10 years. BOWR resulted in the resumption of menstrual cyclicity in 91.1% (82/90) of the cases. However, within this ovulatory group, 26 patients were characterized by oligo-ovulation and a significantly reduced conception rate (29.2%), as compared with that of 56 normo-ovulatory counterparts (60.3%). Although the crude overall conception rate for this series was 47.8%, the overall cumulative probability of conception at the end of follow-up as determined by life table analysis was 73%. The likelihood of conception at any given point in time was estimated by a monthly fecundability rate of 1.34%. Our findings also indicate that the probability of post-BOWR conception was unaffected by age, race, ward status, or duration of infertility. In contrast, persistent post-BOWR oligo- or anovulation and the presence of concurrent tuboperitoneal disease were reaffirmed as the most important determinants of the likelihood of post-BOWR conception. A minimum incidence of 7.8% was documented for acquired post-BOWR pelvic disease.

The clinical use of clomiphene citrate

Rivo E et al., 1965 · Pacific medicine and surgery

INDUCTION OF OVULATION WITH CLOMIPHENE CITRATE

Naville AH et al., 1964 · Fertil Steril

CLOMIPHENE CITRATE: FURTHER OBSERVATIONS ON ITS USE IN INDUCTION OF OVULATION IN THE HUMAN AND ON ITS MODE OF ACTION

Roy S et al., 1963 · Fertil Steril

Induction of ovulation in the human has been of considerable research interest for several decades. Various hormonal regimens and other procedures have been tried in the past.1 • 2 In spite of all these trials, the problem of ovulatory failure remains a frustrating dilemma for the physician. Recently, the induction of ovulation with clomiphene citrate in about 70% of anovulatory women was reported by our group.3- 6 It was felt that an important breakthrough in this difficult field of endeavor was at hand. 7- 9 Our observations have been confirmed by other groups of investigators.10- 12 The present report embodies a detailed analysis of the results of administration of this agent to 200 women, of whom 179 were anovulatory. The results of our studies on the probable mode of action of this drug are also discussed.

Further clinical experience with clomiphene citrate

Macgregor AH et al., 1968 · Fertil Steril