Conservative surgery for ovarian torsion in young women: perioperative complications and national trends.

OBJECTIVE: To analyse populational trends and perioperative complications following conservative surgery versus oophorectomy in women <50 years of age with ovarian torsion. DESIGN: Population-based retrospective observational study. SETTING: Nationwide Inpatient Sample in the USA (2001-2015). POPULATION: In all, 89 177 ovarian torsions including 20 597 (23.1%) conservative surgeries and 68 580 (76.9%) oophorectomies. METHODS: (1) Trend analysis to assess utilisation of conservative surgery over time, (2) multivariable binary logistic regression to identify independent factors associated with conservative surgery and (3) inverse probability of treatment weighting with a generalised estimating equation to analyze perioperative complications. MAIN OUTCOME MEASURES: Trends, characteristics and complications related to conservative surgery. RESULTS: Performance of conservative surgery increased from 18.9 to 25.1% between 2001 and 2015 (32.8% relative increase, P = 0.001) but decreased steadily after age 15, and sharply declined after age 35 (P < 0.001). On multivariable analysis, younger age exhibited the largest effect size for conservative surgery among the independent factors (adjusted odds ratios 3.39-7.96, P < 0.001). In the weighted model, conservative surgery was associated with an approximately 30% decreased risk of perioperative complications overall (10.0% versus 13.6%, odds ratio 0.73, 95% confidence interval 0.62-0.85, P < 0.001) and was not associated with venous thromboembolism (0.2 versus 0.3%, P = 0.457) or sepsis (0.4 versus 0.3%, P = 0.638). CONCLUSION: There has been an increasing utilisation of conservative surgery for ovarian torsion in the USA in recent years. Our study suggests that conservative surgery for ovarian torsion may not be associated with increased perioperative complications. TWEETABLE ABSTRACT: Conservative surgery for ovarian torsion may not be associated with increased perioperative complications.

The ovarian contribution to peripherally derived serum C19 conjugates.

While serum markers of peripheral androgen metabolism, such as 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (3 alpha-diolG) and androsterone glucuronide (AoG), have been highly correlated with adrenal androgen production, the relative ovarian contribution to the pool of various C19 conjugates has not been fully investigated. Our hypothesis was that whereas the ovary may not produce C19 conjugates directly, ovarian androgens, such as testosterone (T) and androstenedione (A), may be used as substrate for peripheral production of these conjugates. To determine whether the ovary contributes directly to the pool of C19 conjugates, blood was obtained from the ovarian and peripheral veins of eight normal women (NW) at hysterectomy. To assess the indirect ovarian contribution to C19 conjugate production, the effect of ovarian suppression and stimulation on circulating 3 alpha-diol and Ao conjugate levels was examined in 10 NW and 10 anovulatory nonhirsute patients with PCO (NH-PCO). Ovarian suppression was carried out with leuprolide acetate (1 mg, sc) daily until the serum estradiol level was 30 pg/mL and was continued thereafter during ovarian stimulation with im human menopausal gonadotropin or FSH. Blood samples were taken before, during, and after GnRH agonist suppression and just before hCG stimulation. Both unconjugated and conjugated androgens were quantified in serum by specific RIAs. No peripheral-ovarian gradients were found for 3 alpha-diol or Ao sulfates (3 alpha-diolS or AoS) or glucuronides. In the NH-PCO group, both T and A levels were elevated, and they were suppressed significantly to levels similar those in NW. With stimulation, T and A levels rose significantly to higher levels than those observed in NW. Both AoS and 3 alpha-diolS, but not AoG and 3 alpha-diolG, decreased significantly with agonist suppression in the two groups; the decrease in levels of AoS and T correlated significantly in the NH-PCO group. With stimulation, the Ao and 3 alpha-diol conjugate levels increased significantly in NH-PCO and were most marked for Ao S and 3 alpha-diol S, which were previously suppressed; the increase in AoG and A correlated highly. Our data suggest that while there is no evidence for the direct ovarian production of C19 conjugates, these markers of peripheral androgen action are influenced by precursors from the ovary, principally A and T.

Production of 3 alpha-androstanediol glucuronide in human genital skin.

3 alpha-Androstanediol glucuronide (3 alpha diol-G) is produced extrasplanchnically and is a good clinical marker of androgen action in peripheral tissues. However, the direct formation of androgen glucuronides in peripheral sites such as skin has not been determined in man. Genital skin from 21 premenopausal women and 8 men and foreskin from 6 neonates were incubated with either [14C]testosterone [14C]dihydrotestosterone (DHT) to determine the production of DHT glucuronide and 3 alpha diol-G in skin. After hydrolysis of incubation medium with glucuronidase, followed by extraction and sequential chromatography, constant 3H to 14C ratios of 3 alpha diol confirmed the production of DHT glucuronide and 3 alpha diol-g. The conversion of DHT to 3 alpha diol-G was higher than the conversion from testosterone (P less than 0.05), and conversion was higher in men than in women. These data provide evidence for the direct formation of C19 steroid glucuronides by human skin.

Markedly elevated levels of estrone sulfate after long-term oral, but not transdermal, administration of estradiol in postmenopausal women.

OBJECTIVE: To compare serum estrone sulfate (E1S) levels in postmenopausal women during long-term treatment with commonly prescribed doses of oral and transdermal estradiol (E2). DESIGN: A retrospective study performed in a University setting in the United States involving 33 healthy postmenopausal women. Two groups of postmenopausal women were studied: group 1 (n = 10) received 1 mg oral micronized E2 daily for 16 months; blood was drawn at 0, 7, and 15 months. Group 2 (n = 23) was randomized into three subgroups. Two of the subgroups (n = 8; n = 7) received E2 delivered at a rate of 0.05 mg/day and 0.1 mg/day, respectively, by transdermal patch, changed twice weekly; the third subgroup received a placebo (without E2) patch for 9 continuous months. Blood samples were drawn at 0, 6, and 9 months. Serum E1S and E2 were quantified by specific radioimmunoassays. Statistical analysis was performed by analysis of variance. RESULTS: After oral E2 treatment, E1S levels increased significantly (p < 0.01) from baseline, reaching an average level of 38.8 ng/mL at 15 months. After transdermal E2 treatment, E1S levels increased significantly, yet to a much lesser extent, reaching levels of 1.8 ng/mL and 3.2 ng/mL after 9 months of treatment with the 0.05 mg/day and 0.1 mg/day patches, respectively. CONCLUSIONS: Markedly elevated levels of E1S were found after long-term oral estrogen treatment. In comparison to the increase in E1S levels after long-term oral estrogen treatment, there was only a small increase in E1S levels after transdermal E2 therapy. This difference may be attributed to the higher dosage of oral E2 that is required because of the low bioavailability compared with the transdermal dosages.

Counseling the infertile couple: when enough is enough.

Therapy of infertility rarely offers a clear end point for cessation after repeated failure. Yet fertility treatment, especially if repeatedly unsuccessful, is associated with economic as well as emotional cost. Stopping treatment becomes an increasingly important option for couples whose therapy does not produce the desired result. It is the clinician's obligation to make infertile couples aware of this option early in the treatment plan and to give specific suggestions that allow these couples to stop treatment at a medically arbitrary, yet temporally well-defined point. To this end, we suggest the following for infertile couples undergoing treatment: 1) an ongoing relationship with a qualified counselor; 2) the best estimates for pregnancy rates, including the background (treatment-independent) rate, for all forms of treatment available at any point in time; 3) the option of stopping treatment from the start; 4) encouragement to seek second opinions throughout treatment; 5) time off from treatment; and 6) the opportunity to set arbitrary but relatively firm time limits. Incorporation of these suggestions into the therapeutic plan for infertile couples underscores the imperfect nature of infertility treatment and acknowledges that sometimes the most we can do for our patients is to help them stop.

In vitro fertilization in unstimulated cycles: a clinical trial using hCG for timing of follicle aspiration.

In vitro fertilization (IVF) was performed in normally ovulatory women after the follicular phase of an unstimulated cycle. Twenty patients initiated 36 cycles of unstimulated IVF, with serial ultrasound examinations and hCG 10,000 IU given when the follicle was mature. Thirty aspirations were carried out under intravenous sedation with transvaginal ultrasound guidance. One or more oocytes were obtained in 29 aspirations (97%) for a total of 52 oocytes (average 1.7); 37 fertilized (71%), two were polyspermic, and 35 cleaved (67%). Seventeen aspirations (57%) yielded multiple oocytes. All 25 oocytes obtained from dominant follicles fertilized (100%), and 12 of 27 oocytes from secondary follicles fertilized (44%) (P less than .05 versus dominant follicles), with one polyspermic fertilization in each group. Sixteen cycles resulted in a single embryo transfer (ET), eight had two embryos, and one had three embryos transferred (36% multiple ET). Five clinical pregnancies (20% per ET, 17% per retrieval) resulted in four ongoing pregnancies (16% per ET, 13% per retrieval), all singletons. Our results suggest that in selected cases, IVF in unstimulated cycles may be a clinically viable alternative to stimulated cycles, with preliminary success rates in the range of national averages for stimulated cycles.

Effects of sex steroids on skin 5 alpha-reductase activity in vitro.

Skin 5 alpha-reductase activity is the major factor influencing the manifestation of androgen excess. Although oral contraceptives have been useful for the treatment of androgen excess, little is known of the independent effects of the various progestins and estrogens on inhibition of skin 5 alpha-reductase activity. We incubated minces of normal genital and pubic skin with physiologic concentrations of 3H-testosterone to assess 5 alpha-reductase activity by its conversion to 3H-dihydrotestosterone. In separate experiments, 5 alpha-reductase activity was assessed before and after the addition of progesterone, medroxyprogesterone acetate, levonorgestrel, norethindrone, 17 beta-estradiol, and ethinyl estradiol. Progesterone, levonorgestrel, and norethindrone demonstrated 97 +/- 5.3%, 47.9 +/- 6.3%, and 59 +/- 4.6% inhibition, respectively, of genital skin 5 alpha-reductase activity at 10(-4) mol/L (P less than .01). Medroxyprogesterone acetate, however, failed to affect 5 alpha-reductase activity at similar doses. Estradiol exhibited 40.8 +/- 14.2% inhibition at 10(-4) mol/L (P less than .01), whereas ethinyl estradiol at concentrations from 10(-8) to 10(-4) mol/L failed to inhibit 5 alpha-reductase activity. We conclude that progesterone and the 19-nor-derivatives inhibit 5 alpha-reductase activity at high doses, whereas medroxyprogesterone acetate does not. Therefore, the 19-nor-progestin component may expand the usefulness of oral contraceptives in the treatment of hirsutism by an inhibitory action on skin 5 alpha-reductase activity.

Resolution of hormonal markers of ectopic gestation: a randomized trial comparing single-dose intramuscular methotrexate with salpingostomy.

OBJECTIVE: To evaluate resolution of serum hCG and progesterone in patients with ectopic pregnancy receiving single-dose intramuscular (IM) methotrexate as compared with those undergoing laparoscopic salpingostomy. METHODS: In this prospective randomized clinical trial, 75 hemodynamically stable women with a diagnosis of ectopic pregnancy were randomized to treatment with single-dose IM methotrexate (1 mg/kg) or laparoscopic salpingostomy. All women had initial, day 4, and weekly serum hCG and progesterone measurements taken until hCG levels were less than 15 mIU/mL. Methotrexate therapy was repeated if posttreatment day 7 hCG levels did not decrease by 15%, as compared with day 4 levels. Success rate was defined as ectopic resolution without the need for the alternate mode of therapy. RESULTS: Thirty-eight women were randomized to treatment with methotrexate and 37 to laparoscopic salpingostomy. The mean (+/-standard deviation) time required for serum progesterone concentrations to decrease to less than 1.5 ng/mL was significantly less for laparoscopic salpingostomy than for treatment with methotrexate: 7.8+/-1.7 and 17.6+/-2.2 days, respectively (P < .01). Within each treatment group, serum progesterone levels resolved (less than 1.5 ng/mL) more rapidly than did hCG levels (less than 15 mIU/mL) (P < .01). No further treatment was required once serum progesterone levels had decreased to less than 1.5 ng/mL. Success rates were similar in both groups: 94.7% (36 of 38) for methotrexate and 91.4% (33 of 36) for laparoscopic salpingostomy. Mean time required for hCG concentrations to decrease to less than 15 mIU/mL was significantly less for laparoscopic salpingostomy than for methotrexate therapy: 20.2+/-2.7 and 27.2+/-2.3 days, respectively (P < .05). Additional methotrexate injections were required in 15.8% (6 of 38) of women randomized to methotrexate therapy. Initial serum hCG levels for patients receiving additional methotrexate doses were 4830+/-1588 mIU/mL as compared with 2133+/-393 mIU/mL for women receiving only one dose (P = .07). CONCLUSION: Serum progesterone levels of less than 1.5 ng/mL are a good predictor of ectopic pregnancy resolution regardless of treatment, and because its return to normal values occurs more rapidly than that of hCG levels, serum progesterone may be a better marker for predicting successful treatment. Although laparoscopic salpingostomy leads to faster resolution of hormonal markers of ectopic gestation, methotrexate is equally successful for treating small unruptured ectopic pregnancies. Initial hCG levels may be a marker for women requiring additional doses of methotrexate.

Ovarian hyperstimulation complicating the clinical presentation of a pre-existing ectopic pregnancy.

A 32-year-old nulliparous woman underwent hMG induction of superovulation, started on the third day of "menses." The presence of hyperstimulation confused the clinical picture of ectopic pregnancy conceived during the previous cycle. This case illustrates that (1) the clinical findings of hyperstimulation may mask those of ectopic pregnancy; (2) the ovary is not refractory to hMG in the presence of circulating hCG; and (3) an inappropriately high beta-hCG value is suggestive of gestation initiated during a previous cycle.

Ovarian derived prorenin-angiotensin cascade in human reproduction.

OBJECTIVE: To review the available literature concerning the renin-angiotensin system of the human and animal ovary and to outline the clinical relevance of this system. DESIGN: The location, function, and regulation of the components of the ovarian prorenin cascade are described. The possible functions of this system as well as its association with common gynecologic problems are also given. CONCLUSIONS: The ovary contains a complete cascade whose end product is the formation of angiotensin II. Angiotensin II may have a role in steroid synthesis, oocyte maturation, ovulation, and corpus luteum formation. Further, aberrations in this system are associated with ovarian tumors, ectopic pregnancy, pre-eclampsia, and ovarian hyperstimulation syndrome.

Triplet pregnancy following oocyte donation to a functionally agonadal woman.

Reported is the first triplet gestation following oocyte donation to an agonadal woman. The transfer of five ova resulted in implantation of all five, with continued embryonic development in three. Pregnancy support was provided by exogenously administered oral E2 and intramuscular P for 100 days, at which time placental hormone production solely maintained the gestations.

Utility and predictive value of a rapid measurement of urinary pregnanediol glucuronide by enzyme immunoassay in an infertility practice.

STUDY OBJECTIVE: To assess the clinical utility of measuring urinary pregnanediol glucuronide in random samples in an infertility practice. DESIGN: Samples of urine were collected from patients approximately 3 weeks from their last menstrual period to ascertain if ovulation had occurred. Each sample was tested for specific gravity before analyzing for pregnanediol glucuronide. Simultaneous venipuncture was performed to compare results from the urinary assay to quantitative measures of serum progesterone (P). SETTING: All patients were randomly sampled. PATIENTS: Three hundred ninety women undergoing pituitary down regulation with leuprolide acetate were chosen for study because they routinely initiate medication after documentation of ovulation. OUTCOME MEASURES: The performance of the urinary pregnanediol glucuronide was evaluated as to its sensitivity, specificity, predictive value, and test efficiency compared with a serum measurement of 2.5 ng/mL and 10.0 ng/mL. RESULTS: The performance characteristics of the pregnanediol glucuronide assay were directly related to the hydration status of the patient at the time of sample collection. Regardless of urine specific gravity, if pregnanediol glucuronide was qualitatively detected (greater than 3 micrograms/mL), serum P was greater than 2.5 ng/mL. However, in cases in which pregnanediol glucuronide was undetected (less than 3 micrograms/mL), results were only accurate when the specific gravity was greater than or equal to 1.020. When comparing urinary pregnanediol glucuronide values to serum greater than 10 ng/mL, both specificity and predictive value of a positive test decreased because of increased numbers of false-positive results. CONCLUSIONS: The enzyme immunoassay measurement for pregnanediol glucuronide may replace the use of serum P in documenting the ovulatory status of many patients. However, all specimens must be checked for specific gravity and if less than 1.020, a serum P should be used to ensure accuracy.

Mishaps and misfortunes: complications that occur in oocyte donation.

Despite careful screening and the adherence to strict protocol, approximately 2% of initiated cycles of oocyte donation were found to be complicated by difficulties incurred by oocyte donors. The risk of these adverse events appeared to be limited to the initial trial of donation with experienced donors being more reliable. Thus, surveillance of the cycle's progress should be maximal during this time. Both donors and recipients need to be aware of the unique problems posed by oocyte donation to provide full informed consent. This includes the possibility for unplanned pregnancies when discontinuing the donors' usual method of contraception. These mishaps underscore the importance of reminding patients that cycle success cannot be guaranteed, and unexpected complications cannot be entirely avoided.

Follicle aspiration, sperm injection, and assisted rupture (FASIAR): a simple new assisted reproductive technique.

OBJECTIVE: To describe the first successful application of a new fertility-enhancing technique. DESIGN: Case report. SETTING: Academic fertility program. PATIENT(S): A 36-year-old nulligravid woman undergoing inseminations with frozen-thawed donor sperm. INTERVENTION(S): Ovarian superovulation, follicle aspiration, sperm injection, and assisted follicular rupture. MAIN OUTCOME MEASURE(S): Assessment of feasibility of technique and pregnancy outcome. RESULT(S): After failing to conceive during 16 cycles of IUI, the patient successfully achieved an ongoing pregnancy during the second follicle aspiration, sperm injection, and assisted rupture (FASIAR) attempt. CONCLUSION(S): Follicle aspiration, sperm injection, and assisted rupture combines the concepts of superovulation, IUI, and peritoneal oocyte and sperm transfer to obviate the possibility of luteinized unruptured follicle syndrome, assist oocyte release, and ensure gamete intermixing. It also can be used to reduce the number of ovulating oocytes and thus to reduce the risk of multiple gestations. Follicle aspiration, sperm injection, and assisted rupture is a new, simple, office-based procedure that does not require embryologic expertise beyond sperm preparation as for IUI, yet promises to be more successful than IUI.

Increased angiotensin-converting enzyme activity in a patient with severe ovarian hyperstimulation syndrome.

OBJECTIVE: To assess plasma angiotensin-converting enzyme (ACE) activity in a patient with severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Case report. SETTING: Private, university-affiliated infertility practice. PATIENT(S): A 35-year-old woman with OHSS. INTERVENTION(S): Clomiphene citrate induction of ovulation. MAIN OUTCOME MEASURE(S): Plasma ACE activity. RESULT(S): The patient had a brain stem infarction as a result of thrombosis caused by severe OHSS. Plasma ACE activity was significantly elevated and persisted long after resolution of the OHSS. CONCLUSION(S): Elevated ACE activity appears to have been associated with the development of OHSS in this patient. Further study of the ovarian renin-angiotensin system in the development of OHSS is warranted.

Ultrastructural characteristics of the luteal phase endometrium in patients undergoing controlled ovarian hyperstimulation.

OBJECTIVE: To provide a descriptive analysis of the ultrastructure of the endometrial surface epithelium during the luteal phase from patients undergoing controlled ovarian hyperstimulation (COH). DESIGN: Prospective, observational study. SETTING: Tertiary care academic IVF center. PATIENT(S): Twelve oocyte donors undergoing COH. INTERVENTION(S): After oocyte aspiration, patients underwent two endometrial biopsies 2 to 7 days after hCG administration. MAIN OUTCOME MEASURE(S): Appearance of the endometrial epithelial surface as evaluated by scanning electron microscopy. RESULT(S): Endometrial maturation proceeded in an orderly manner. The ciliated cells remained unchanged, both in regards to cell density, cilia density, and ratio of ciliated cells to nonciliated cells. The microvilli became more uniformly distributed as the luteal phase progressed. The central aspect of the cells also appeared to protrude more into the endometrial lumen as the cycle progressed. Elongation the glandular orifices also was noted with progression of the luteal phase. Apical protrusions, pinopods, were noted to develop and regress during a short period during the midluteal phase spanning days 4 to 7 after hCG administration. Initial pinopod development began in the region of the glandular orifices, with substantially fewer occurring outside this region. CONCLUSION(S): Although the development of the endometrial ultrastructural characteristics during the luteal phase progresses in an orderly manner that is comparable to that of endometrium obtained in unstimulated cycles, pinopod expression was noted at an earlier phase of endometrial maturation. This advanced development may result in an alteration the window of implantation and affect pregnancy rates in women undergoing COH.

Comparison of two methods for the measurement of sperm concentration.

OBJECTIVE: To determine the accuracy of both the hemocytometer and the MicroCell, to evaluate which method is the most reliable, and to confirm the accuracy of latex beads as an internal standard. DESIGN: Prospective procedural assessment. SETTING: University-based infertility clinic. PATIENT(S): One hundred sixty-five male sexual partners of women undergoing screening for infertility. INTERVENTION(S): Semen analysis. MAIN OUTCOME MEASUREMENT(S): Sperm and latex bead concentrations. RESULT(S): Sperm concentration values obtained with the hemocytometer were highly correlated with those obtained from the MicroCell (r = 0.88). The mean value of the latex beads concentration was closer to the standard value using the hemocytometer than the MicroCell. CONCLUSION(S): Both the hemocytometer and the MicroCell are suitable as screening techniques to measure sperm concentration. Fixed suspensions of latex beads serve as reliable internal quality control standards.

Very high serum estradiol levels are not detrimental to clinical outcome of in vitro fertilization.

The use of gonadotropin-releasing hormone agonists as adjuncts to ovulation induction for in vitro fertilization (IVF) has resulted in increases in oocyte recovery rates. Along with increased oocyte number, greatly increased estradiol (E2) levels have been found. We sought to determine the clinical effect of very high E2 levels on the outcome of IVF cycles. Estradiol levels were measured in 141 patients undergoing controlled ovarian hyperstimulation with leuprolide acetate and human menopausal gonadotropin for IVF. Whereas the number of oocytes recovered and fertilized and the number of embryos available for cryopreservation were directly proportional to the E2 level, the fertilization rate and embryo cleavage rates were unrelated to the E2 level. When the patients were grouped in thirds according to E2 levels, pregnancy rate (PR) was highest in the patients with the highest E2 levels (E2 greater than 2,777 pg/mL, PR = 37%). One mild, one moderate, and one severe case of ovarian hyperstimulation syndrome occurred in patients with E2 greater than or equal to 3,000 pg/mL (n = 21), but in general, high E2 levels were attained with few complications. We conclude that high E2 levels are not detrimental to the pregnancy outcome of IVF. Our experience further suggests that cycles with E2 levels of less than or equal to 5,000 pg/mL need not be canceled and can proceed to oocyte recovery and embryo transfer.

Pregnancy after in vitro fertilization in a patient with stage I endometrial carcinoma treated with progestins.

A 35-year-old woman with chronic anovulation and bilateral tubal disease was found during infertility evaluation to have grade I endometrial carcinoma confined to an endometrial polyp. She was treated with polypectomy and endometrial curettage followed by high-dose progestagens for 6 months. Endometrial curettage at 3 and 6 months of therapy indicated regression of the lesion and the patient subsequently achieved successful pregnancy with IVF.

Mouse embryo culture as quality control for human in vitro fertilization: the one-cell versus the two-cell model.

Female mice were superovulated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) and mated with male mice. One-cell (n = 429) and 2-cell (n = 450) embryos were collected 20 and 42 hours after hCG and cultured in Ham's F-10 medium (Gibco, Grand Island, NY) (282 mOsm/l, pH 7.4) and in media of altered osmolality (260, 300, 316 mOsm/l), altered pH (7.0, 7.8, 8.0) or various dilutions of Cidex (Surgikos, Arlington, TX) (1:1000, 1:10,000, 1:100,000). Stages of development were observed for 4 days. The development of embryos in the 1-cell system was significantly impaired under all studied conditions by the 4-cell stage of development. The 2-cell system failed to detect trace amounts of Cidex in the culture media and an increase in osmolality to 300 mOsm/l. Other changes in osmolality (260 mOsm/l) and pH (7.8) were detected by the 2-cell system only at the blastocyst stage. The authors conclude that the 1-cell system is more sensitive than the 2-cell system to mild changes in in vitro fertilization culture media.