Faculty Bibliography

OBJECTIVE:To assess the efficacy of human embryo twinning by blastomere biopsy at different early embryonic stages (splitting efficiency) and to determine the in vitro developmental capacity of twinned human embryos (developmental efficiency). DESIGN/METHODS:Randomized comparative study. SETTING/METHODS:Private IVF centers. PATIENT(S)/METHODS:Couples undergoing IVF donating triploid embryos. INTERVENTION(S)/METHODS:Embryos at the 2- to 5- and 6- to 8-cell stage were split into twin embryos. Half the number of blastomeres from donor embryos were removed and inserted into recipient empty zonae pellucidae. After embryo splitting, donor and recipient embryos were cultured in vitro. MAIN OUTCOME MEASURE(S)/METHODS:Development of twinned embryos to the blastocyst stage. RESULT(S)/RESULTS:The number of developing embryos obtained after splitting could be increased in comparison with the number of embryos available before splitting at the 6- to 8-cell stage but not at the 2- to 5-cell stage (splitting efficiency). Splitting of 6- to 8-cell embryos yielded superior rates of twin embryos developing to blastocysts (developmental efficiency). Twinning success was related to the superior morphological quality of embryos used for splitting. CONCLUSION(S)/CONCLUSIONS:This is the first report on twinned human embryos developing to blastocysts. This study exhibits the potential for novel applications in human assisted reproduction.

BACKGROUND:Leiomyomatosis peritonealis disseminata has been attributed to estrogen stimulation and is seen only rarely in postmenopausal women. In such cases, pathogenesis is uncertain. CASE/METHODS:Leiomyomatosis peritonealis disseminata tumors were resected from a postmenopausal woman. She was receiving tamoxifen therapy for breast cancer and had bilateral ovarian Brenner tumors. Estrogen and progesterone receptors were detected. Immunohistochemical analysis indicated that LH receptors were present. CONCLUSION/CONCLUSIONS:Luteinizing hormone receptors were identified in leiomyomatosis peritonealis disseminata in one woman. Levels of FSH and LH increase after menopause, and immunohistochemical analysis showed the presence of LH receptors, so gonadotropin rather than estrogen stimulation might have contributed to development of leiomyomatosis peritonealis disseminata in this uncommon case.

OBJECTIVE:To evaluate the outcome of IVF-ET after the use of Crinone 8% (Wyeth-Ayerst Laboratories, Inc., Philadelphia, PA) vaginal progesterone gel and to compare these results with those seen in our program with the use of IM progesterone-in-oil. DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:A tertiary referral reproductive medicine unit. PATIENT(S)/METHODS:Patients <40 years of age undergoing IVF-ET cycles. INTERVENTION(S)/METHODS:Patients were treated with either Crinone 8% vaginal progesterone gel (90 mg) administered daily or IM progesterone-in-oil (50 mg) administered daily. MAIN OUTCOME MEASURE(S)/METHODS:Biochemical pregnancy rate, implantation rate, and clinical and ongoing pregnancy rates. RESULT(S)/RESULTS:The use of Crinone 8% vaginal progesterone gel was associated with a lower implantation rate (16.6% versus 26.2%; odds ratio [OR] = 0.56; 95% confidence interval [CI], 0.35-0.89) compared with the use of IM progesterone-in-oil. Biochemical pregnancies were more common after the use of Crinone 8% vaginal progesterone gel as defined by either biochemical pregnancies per transfer (15.9% versus 5.7%; OR = 3.11; 95% CI, 1.17-8.32) or biochemical pregnancies as a proportion of positive serum hCG titers (29.2% versus 9.8%; OR = 3.80; 95% CI, 1.33-10.86). Clinical pregnancy rates also were lower with the use of Crinone 8% vaginal progesterone gel (36.4% versus 52.9%; OR = 0.51; 95% CI, 0.26-0.99). CONCLUSION(S)/CONCLUSIONS:Implantation efficiency is reduced, as demonstrated by lower embryonic implantation rates and higher biochemical pregnancy rates, when Crinone 8% vaginal progesterone gel rather than IM progesterone-in-oil is used for luteal phase support after IVF-ET.

The cervical canal is difficult to visualize during hysteroscopy, making hysteroscopic maneuvers difficult. In our patient, after traditional surgical approaches failed, we used a polyp snare and closed the outflow channel of the hysteroscope, which allowed rapid removal of a cervical polyp in its entirety. This is an effective technique for excising intracervical lesions. (J Am Assoc Gynecol Laparosc 6(2):201-203, 1999)

OBJECTIVE:To examine the relation between blood found on the transfer catheter after ET and the rates of embryo implantation and clinical pregnancy with the use of IVF-ET. DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:A tertiary care center for assisted reproductive technology. PATIENT(S)/METHODS:Three hundred seven couples who underwent 354 ETs between January 1, 1994, and June 30, 1996. INTERVENTION(S)/METHODS:A semiquantitative system for recording the amount of blood found inside and outside the transfer catheter after ET. MAIN OUTCOME MEASURE(S)/METHODS:Embryo implantation rate and clinical pregnancy rate (PR). RESULT(S)/RESULTS:Blood found outside the transfer catheter after ET was associated with decreased rates of embryo implantation and clinical pregnancy. In contrast, blood located inside the transfer catheter after ET, the type of catheter used for ET, the number of transfer attempts, and the time required for ET did not significantly affect either the embryo implantation rate or the clinical PR. CONCLUSION(S)/CONCLUSIONS:Blood found outside, but not inside, the transfer catheter after ET is associated with lower rates of embryo implantation and clinical pregnancy with the use of IVF-ET. An emphasis on atraumatic transfer techniques, with prevention of bleeding at the time of ET, should contribute to improved pregnancy outcome with the use of IVF-ET.

BACKGROUND:Ultrasound guidance has been recommended for various operative hysteroscopic procedures as an alternative to laparoscopic guidance. Ultrasound is noninvasive and may decrease the incidence of uterine perforation. CASE/METHODS:A 30-year-old nulligravida presented for the evaluation of amenorrhea of two months' duration. She was diagnosed as having cervical obstruction and underwent operative hysteroscopy with cervical cannulation under ultrasound guidance. The patient's menstrual flow returned at the appropriate time without dysmenorrhea. CONCLUSION/CONCLUSIONS:Ultrasound guidance during hysteroscopy assisted in the proper orientation and position of the hysteroscope at the time of cannulation, potentially minimizing the risk of uterine perforation.

The cardinal clinical features of PCOS are hirsutism and menstrual irregularity from anovulation. Obesity occurs in approximately 50% of hyperandrogenic anovulatory women, some of whom also have non-insulin-dependent diabetes mellitus. Underlying these clinical findings are several biochemical abnormalities, including LH hypersecretion, hyperandrogenism, acyclic estrogen production, decreased SHBG capacity, and hyperinsulinemia, all of which contribute to increased ovarian production of androgens, particularly T. A fundamental mechanism of ovarian hyperandrogenism in PCOS is LH hypersecretion. Whether the central nervous system is a possible locus for initiating LH hypersecretion remains unclear, because exaggerated LH secretion is temporarily reversed by induced ovulatory cycles or physiologic luteal concentrations of progesterone. On the other hand, desynchronization of pulsatile LH secretion from sleep in girls with PCOS and an exaggerated (e.g., masculinized) early LH response to GnRHa testing in women with hyperandrogenic anovulation and congenital adrenal virilizing disorders suggest that events occurring before puberty, perhaps during fetal life, may irreversibly alter neuroendocrine function. Hyperinsulinemia from insulin resistance is an important regulatory mechanism governing ovarian hyperandrogenism. Hyperinsulinemia in hyperandrogenic anovulatory women potentiates ovarian hyperandrogenism by enhancing LH secretion; potentiating 17-hydroxylase and, to a lesser extent, 17,20-lyase activity; and suppressing SHBG capacity. It is a key component of hyperandrogenic anovulation caused by a type of insulin resistance that in independent and additive to that of obesity alone. Although the mechanisms governing insulin action on ovarian steroidogenesis are unknown, abnormalities of intracellular insulin signaling or cytochrome P450c 17[alpha] activity may render the 17-hydroxylase/17,20-lyase enzyme complex more sensitive to insulin. Hyperinsulinemia in hyperandrogenic anovulatory women is accompanied by upper-body obesity characterized by an increased amount of abdominal fat. Upper-body obesity is an important independent risk factor for CVD and diabetes. Although genetic and environmental factors affect fat distribution, sex steroids, particularly androgens, regulate lipid metabolism, suggesting yet another link between the hormonal and metabolic abnormalities of hyperandrogenic anovulation. A careful history and physical examination guide the extent of diagnostic testing. Slowly progressive hirsutism with anovulation of peripubertal onset usually reflects hyperandrogenic anovulation. This type of clinical presentation requires an evaluation to rule out other endocrinopathies (e.g., virilizing tumors, adult-onset CAH, hyperprolactinemia, and Cushing's syndrome). Virilization or severe rapidly progressive hirsutism requires immediate investigation to rule out a possible virilizing tumor. The ultimate goals of therapy for hyperandrogenic anovulatory women are to normalize the endometrium, antagonize androgen action at target tissues, reduce insulin resistance, and correct anovulation, if necessary.

BACKGROUND:Hormone production is a characteristic associated with the presence of solid tumors in the ovary. We present a case of a solitary ovarian cyst producing large amounts of testosterone and presenting with rapid onset of hirsutism. CASE/METHODS:A woman presented approximately 6 months postpartum with irregular menses and rapid onset of hirsutism. Laboratory and radiologic evaluation indicated an ovarian cyst as the source. On removal, the cyst was found to have high amounts of testosterone in its fluid and the surrounding stroma had nests of luteinized cells. CONCLUSION/CONCLUSIONS:The chronic anovulation in the postpartum period may have prolonged the lifespan of the luteinized stromal cells, resulting in high levels of circulating testosterone and causing rapid progression of hirsutism.