Susan B. Hudson

Treatment of ovarian hyperstimulation syndrome using a dopamine agonist and gonadotropin releasing hormone antagonist: a case series

OBJECTIVE To describe an outpatient treatment protocol for ovarian hyperstimulation syndrome (OHSS) that results in rapid normalization of symptoms with minimal side effects. DESIGN Case series. SETTING Midwestern academic reproductive endocrinology division. PATIENT(S) Four consecutive patients, diagnosed with OHSS, who presented after oocyte retrieval but before embryo transfer. INTERVENTION(S) All embryos were frozen and each patient was treated with the same dopamine agonist and GnRH antagonist protocol. MAIN OUTCOME MEASURE(S) Daily weights, days to resolution of clinical symptoms, side effects of the treatment protocol, and whether or not acute care or hospitalization was necessary. RESULT(S) The most rapid weight loss was within the first 5 days of treatment. The average time to resolution of clinical symptoms was 5.75 days. No side effects were reported and no patients required acute care or hospitalization. CONCLUSION(S) Dopamine agonists and GnRH antagonists, when given together at the time of diagnosis of OHSS, appear to work rapidly and effectively to diminish the clinical symptoms of the disease. The potential benefit of finding an outpatient treatment for OHSS with rapid onset and minimal side effects warrants further investigation into this protocol.

Peroxides in mineral oil used for in vitro fertilization: defining limits of standard quality control assays

PurposeTo determine the relative sensitivities of the 1 and 2-cell mouse embryo assays (MEA) and the human sperm motility assay (HSMA) for peroxides in mineral oil. The effect of peroxide on blastocyst cell number and apoptosis was also studied.MethodsOne and two-cell MEA and HSMA were performed using mineral oil containing cumene hydroperoxide (CH).ResultsThe 1-cell MEA was twice as sensitive as the 2-cell MEA and 20-times more sensitive than the HSMA for CH in mineral oil. The sensitivity of the 1-cell MEA doubled when embryos were cultured individually versus group culture. CH decreased blastocyst cell number in a dose dependent manner.ConclusionsIndividually cultured 1-cell embryos had the highest sensitivity for peroxides in mineral oil. Current quality control assays, including group cultured murine embryos and human sperm motility, have limited sensitivity for peroxides in mineral oil and may not detect levels of peroxides that cause sub-lethal cellular damage.

Ovarian stromal hyperthecosis: Sonographic features and histologic associations

Objective. Ovarian stromal hyperthecosis (SH) has variable clinical importance but can cause hyperandrogenism, particularly in premenopausal women. Sonography is often used to evaluate the ovaries of women with hyperandrogenism, but there is little published regarding the sonographic appearance of SH. The primary purpose of this study was to describe the sonographic features of SH. Methods. A computerized search of our institutions pathology and imaging databases from 1996 through 2007 was performed to identify patients with histologically proven SH who had pelvic sonography before surgery. Sonograms and histologic findings were reviewed in each case. Results. Twenty ovaries with SH were identified, occurring in 14 patients with a mean age of 59.8 years (range, 36–83 years). The SH was bilateral in 6 patients, unilateral in 6, and of uncertain laterality in 2 with a unilateral oophorectomy. Sonographic findings were as follows: 5 normal, 1 with a hemorrhagic cyst (later resolved) and otherwise normal, 3 enlarged but otherwise normal, 1 with a solid mass due to the nodular form of SH, 1 with a solid mass due to a fibroma, 2 with polycystic ovaries, and 7 not seen. Six of the 14 patients (43%) also had an ovarian fibrothecoma. Conclusions. Ovarian SH has variable sonographic features. Most commonly, the affected ovaries are either normal or slightly enlarged. A solid mass may infrequently be visible, and polycystic ovary syndrome changes may coexist with SH. A possible association of SH with fibrothecoma was also noted, which to our knowledge has not been previously reported.

Relative effects of estrogen, age, and visceral fat on pulsatile growth hormone secretion in healthy women

Growth hormone (GH) secretion is subject to complex regulation. How pre- and postmenopausal age (PRE, POST), estradiol (E(2)) availability, and abdominal visceral fat (AVF) jointly affect peptidyl-secretagogue drive of GH secretion is not known. To this end, healthy PRE (n = 20) and POST (n = 22) women underwent a low- vs. high-E(2) clamp before receiving a continuous intravenous infusion of GH-releasing hormone (GHRH) or GH-releasing peptide (GHRP-2). According to analysis of covariance, PRE and POST women achieved age-independent hypo- and euestrogenemia under respective low- and high-E(2) clamps. All four of age (P < 0.001), E(2) status (P = 0.006), secretagogue type (P < 0.001), and an age x peptide interaction (P = 0.014) controlled pulsatile GH secretion. Independently of E(2) status, POST women had lower GH responses to both GHRH (P = 0.028) and GHRP-2 (P < 0.001) than PRE women. Independently of age, GHRP-2 was more stimulatory than GHRH during low E(2) (P = 0.011) and high E(2) (P < 0.001). Stepwise forward-selection multivariate analysis revealed that computerized tomographic estimates of AVF explained 22% of the variability in GHRH action (P = 0.002), whereas age and E(2) together explained 60% of the variability in GHRP-2 drive (P < 0.001). These data establish that age, estrogen status, and AVF are triple covariates of continuous peptide-secretagogue drive of pulsatile GH secretion in women. Each factor must be controlled for to allow valid comparisons of GH-axis activity.

Pre- Versus Postmenopausal Age, Estradiol, and Peptide-Secretagogue Type Determine Pulsatile Growth Hormone Secretion in Healthy Women: Studies Using Submaximal Agonist Drive and an Estrogen Clamp

CONTEXT GH-releasing peptide (GHRP), GHRH, and somatostatin are physiological regulators of pulsatile GH secretion. HYPOTHESIS Age, independently of abdominal visceral fat (AVF) and basal (nonpulsatile) GH secretion, damps pulsatile GH secretion driven by physiological (rather than pharmacological) amounts of GHRP and GHRH in an experimentally controlled estradiol (E(2)) milieu. DESIGN AND SETTING A prospectively randomized, double-blind parallel-cohort study was conducted at an academic medical center. PARTICIPANTS Community-dwelling healthy premenopausal (PRE, age 24 +/- 0.8 yr, n = 20) and postmenopausal (POST, age 63 +/- 1.8 yr, n = 22) women participated in the study. INTERVENTIONS Gonadal-axis down-regulation with leuprolide was followed by randomized addback of placebo or transdermal E(2) and separate-day iv bolus injections of a half-maximally stimulatory dose of GHRP-2 or GHRH (each 0.33 mug/kg). ANALYSIS Three-way analysis of covariance included main factors age, E(2) status, and secretagogue type and covariates AVF and basal GH secretion. RESULTS Submaximally stimulated pulsatile GH secretion was positively determined by PRE vs. POST age (P < 0.001), E(2) repletion vs. depletion (P = 0.001) and GHRP-2 vs. GHRH stimulation (P < 0.001), after adjustment for AVF and basal secretion. E(2) vs. placebo elevated fasting mean GH concentrations in both PRE and POST women (P = 0.006) but increased basal (nonpulsatile) GH secretion in PRE only (P = 0.002). PRE vs. POST age prolonged GHRH-driven GH secretory bursts by 36% (P = 0.006). CONCLUSION PRE vs. POST age, E(2) availability, and physiological peptide drive are triple determinants of pulsatile GH secretion independently of abdominal visceral fat and nonpulsatile GH secretion in healthy women.

Magnetic Resonance- guided Focused Ultrasound Surgery

Uterine leiomyomas pose a significant health issue to reproductive-age women. Many women desire uterine conservation, and previously safe and efficacious therapies have been limited. Magnetic resonance-guided focused ultrasound surgery is a new noninvasive therapy that has been proven to be both safe and efficacious in the treatment of fibroids.

High Cumulative Live Births in Oocyte Donation Cycles with Cryopreservation of All Embryos

Background: Cryopreservation of all embryos in stimulated IVF cycles is occasionally necessary. Although it is known that frozen embryo transfer results in lower live birth rates per transfer, there is limited information regarding expected cumulative live birth rates for patients who are in this particular scenario. Methods: The objective was to evaluate long-term outcomes in cycles undergoing pronuclear cryopreservation of all embryos utilizing a retrospective analysis of 154 consecutive recipients from 1995 to 2006. Results: The cumulative rate of first live birth per retrieval was 66.2%, with a 36.4% live birth rate per frozen embryo transfer. Following an average 2.2 ± 0.98 transfers, 32.6% (17/52) of patients who never delivered had remaining embryos making the cumulative first live birth rate previously stated a conservative estimate. 11.7% of recipients had sibling deliveries from a single retrieval. Over 1/3 of the delivered recipients have remaining cryopreserved embryos and could pursue an additional pregnancy. Conclusion: These results suggest that pronuclear cryopreservation of all embryos in an oocyte donation cycle maintains good cumulative live birth rates, as well as chances for a sibling from a single retrieval. Recipients who must delay transfer can be reassured a high potential for live birth from their first donor retrieval.

Preimplantation genetic screening in a case of recurrent trisomy 21 offspring.

OBJECTIVE To describe a unique case of recurrent aneuploidy and the use of preimplantation genetic screening (PGS). DESIGN Case report. SETTING Midwest academic medical center. PATIENT(S) A 36-year-old woman with two trisomy 21 offspring. INTERVENTION(S) Preimplantation genetic screening. MAIN OUTCOME MEASURE(S) Karyotype of embryos, liveborn eukaryotic infant. RESULT(S) Preimplantation genetic screening was performed on three cryopreserved embryos, followed by a two-embryo transfer yielding a eukaryotic infant. CONCLUSION(S) Preimplantation genetic screening may prove to be useful as a diagnostic tool to help ensure a euploid pregnancy when termination is not a viable option for a couple.

OC207: Ovarian stromal hyperthecosis: sonographic features and histological associations

Objectives: Ovarian causes of virilization include polycystic ovary syndrome (PCOS), androgen-secreting neoplasms and ovarian stromal hyperthecosis (SH). The ultrasound features of the first two causes have been described, but there is little published data regarding the ultrasound appearance of ovarian stromal hyperthecosis. The primary purpose of this study was to describe the sonographic features of ovarian SH. Methods: A computerized search of our institution’s pathology and imaging databases from 1996 to 2006 was performed to identify patients with histologically proven SH who had a pelvic ultrasound scan before surgery. The ultrasound images were reviewed to categorize the ultrasound findings. Associated pathological findings in the ovaries and uterus were also noted. Results: Sixteen ovaries with SH, in 12 patients with mean age 59.6 (range, 36–83) years, were identified. SH was bilateral in four, unilateral in six and of uncertain laterality in two patients who only had a unilateral oophorectomy. Ultrasound findings in the 16 ovaries with SH were: two normal, seven not seen, three enlarged but otherwise normal, one with a hemorrhagic cyst (resolved by surgery) and otherwise normal, one with a probable solid mass (nodular SH), and two with polycystic ovaries (both SH and PCOS by histology). Three of the 12 patients (25%) also had endometrial carcinoma. Five of the 12 patients (42%) also had an ovarian fibrothecoma. Conclusions: Ovarian SH does not have recognizable ultrasound findings in most patients. A minority of affected ovaries appear enlarged but otherwise normal, a solid mass may infrequently be visible, and PCOS changes may coexist with SH. A possible association of SH with endometrial carcinoma was noted, and has been reported previously. A possible association of SH with fibrothecoma was also noted, which to our knowledge has not been reported previously.