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Study Objective: To evaluate the use of a technique consisting of culdocentesis followed by saline solution-enhanced pelvic ultrasonography in cases suspect for ectopic pregnancy in which an accurate diagnosis could not be made using routine transvaginal ultrasound. Design: Retrospective clinical study (Canadian Task Force classification III). Setting: Academic medical center. Patients: Twenty patients with an initial diagnosis of pregnancy of unknown location. Interventions: In 20 patients with symptoms of early pregnancy and serum quantitative human chorionic gonadotropin concentration, ectopic pregnancy could not be confirmed or ruled out. Transvaginal ultrasound-guided culdocentesis was performed, and 300 to 400 mL of normal saline solution was injected into the posterior cul-de-sac and pelvis. Transvaginal ultrasound was repeated with particular attention to the floating fallopian tubes Measurements and Main Results: Using this technique, a tubal pregnancy was visualized in 15 of 20 patients, and ectopic pregnancy was ruled out in 5 patients. In all patients, appropriate management was provided according to the final diagnosis, and consisted of either methotrexate, laparoscopic salpingostomy or salpingectomy, or expectant management in patients with abnormal intrauterine pregnancies. Conclusion: Ultrasound-guided culdocentesis followed by saline solution-enhanced pelvic ultrasound can be considered as a diagnostic tool in patients with suspected ectopic pregnancy in whom other methods fail to demonstrate this diagnosis. [ABSTRACT FROM AUTHOR]

Study Question: Is salpingotomy cost effective compared with salpingectomy in women with tubal pregnancy and a healthy contralateral tube?, Summary Answer: Salpingotomy is not cost effective over salpingectomy as a surgical procedure for tubal pregnancy, as its costs are higher without a better ongoing pregnancy rate while risks of persistent trophoblast are higher., What Is Known Already: Women with a tubal pregnancy treated by salpingotomy or salpingectomy in the presence of a healthy contralateral tube have comparable ongoing pregnancy rates by natural conception. Salpingotomy bears the risk of persistent trophoblast necessitating additional medical or surgical treatment. Repeat ectopic pregnancy occurs slightly more often after salpingotomy compared with salpingectomy. Both consequences imply potentially higher costs after salpingotomy., Study Design, Size, Duration: We performed an economic evaluation of salpingotomy compared with salpingectomy in an international multicentre randomized controlled trial in women with a tubal pregnancy and a healthy contralateral tube. Between 24 September 2004 and 29 November 2011, women were allocated to salpingotomy (n = 215) or salpingectomy (n = 231). Fertility follow-up was done up to 36 months post-operatively., Participants/materials, Settings, Methods: We performed a cost-effectiveness analysis from a hospital perspective. We compared the direct medical costs of salpingotomy and salpingectomy until an ongoing pregnancy occurred by natural conception within a time horizon of 36 months. Direct medical costs included the surgical treatment of the initial tubal pregnancy, readmissions including reinterventions, treatment for persistent trophoblast and interventions for repeat ectopic pregnancy. The analysis was performed according to the intention-to-treat principle., Main Results and the Role of Chance: Mean direct medical costs per woman in the salpingotomy group and in the salpingectomy group were €3319 versus €2958, respectively, with a mean difference of €361 (95% confidence interval €217 to €515). Salpingotomy resulted in a marginally higher ongoing pregnancy rate by natural conception compared with salpingectomy leading to an incremental cost-effectiveness ratio €40 982 (95% confidence interval -€130 319 to €145 491) per ongoing pregnancy. Since salpingotomy resulted in more additional treatments for persistent trophoblast and interventions for repeat ectopic pregnancy, the incremental cost-effectiveness ratio was not informative., Limitations, Reasons for Caution: Costs of any subsequent IVF cycles were not included in this analysis. The analysis was limited to the perspective of the hospital., Wider Implications of the Findings: However, a small treatment benefit of salpingotomy might be enough to cover the costs of subsequent IVF. This uncertainty should be incorporated in shared decision-making. Whether salpingotomy should be offered depends on society's willingness to pay for an additional child., Study Funding/competing Interests: Netherlands Organisation for Health Research and Development, Region Västra Götaland Health & Medical Care Committee., Trial Registration Number: ISRCTN37002267., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Tubal ectopic pregnancy can be surgically treated by salpingectomy, in which the affected Fallopian tube is removed, or salpingotomy, in which the tube is preserved. Despite potentially increased risks of persistent trophoblast and repeat ectopic pregnancy, salpingotomy is often preferred over salpingectomy because the preservation of both tubes is assumed to offer favourable fertility prospects, although little evidence exists to support this assumption. We aimed to assess whether salpingotomy would improve rates of ongoing pregnancy by natural conception compared with salpingectomy., Methods: In this open-label, multicentre, international, randomised controlled trial, women aged 18 years and older with a laparoscopically confirmed tubal pregnancy and a healthy contralateral tube were randomly assigned via a central internet-based randomisation program to receive salpingotomy or salpingectomy. The primary outcome was ongoing pregnancy by natural conception. Differences in cumulative ongoing pregnancy rates were expressed as a fecundity rate ratio with 95% CI, calculated by Cox proportional-hazards analysis with a time horizon of 36 months. Secondary outcomes were persistent trophoblast and repeat ectopic pregnancy (expressed as relative risks [RRs] with 95% CIs) and ongoing pregnancy after ovulation induction, intrauterine insemination, or IVF. The researchers who collected data for fertility outcomes were masked to the assigned intervention, but patients and the investigators who analysed the data were not. All endpoints were analysed by intention to treat. We also did a (non-prespecified) meta-analysis that included the findings from the present trial. This trial is registered, number ISRCTN37002267., Findings: 446 women were randomly assigned between Sept 24, 2004, and Nov 29, 2011, with 215 allocated to salpingotomy and 231 to salpingectomy. Follow-up was discontinued on Feb 1, 2013. The cumulative ongoing pregnancy rate was 60·7% after salpingotomy and 56·2% after salpingectomy (fecundity rate ratio 1·06, 95% CI 0·81-1·38; log-rank p=0·678). Persistent trophoblast occurred more frequently in the salpingotomy group than in the salpingectomy group (14 [7%] vs 1 [<1%]; RR 15·0, 2·0-113·4). Repeat ectopic pregnancy occurred in 18 women (8%) in the salpingotomy group and 12 (5%) women in the salpingectomy group (RR 1·6, 0·8-3·3). The number of ongoing pregnancies after ovulation induction, intrauterine insemination, or IVF did not differ significantly between the groups. 43 (20%) women in the salpingotomy group were converted to salpingectomy during the initial surgery because of persistent tubal bleeding. Our meta-analysis, which included our own results and those of one other study, substantiated the results of the trial., Interpretation: In women with a tubal pregnancy and a healthy contralateral tube, salpingotomy does not significantly improve fertility prospects compared with salpingectomy., Funding: Netherlands Organisation for Health Research and Development (ZonMW), Region Västra Götaland Health & Medical Care Committee., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The goal of regenerative medicine is to repair, replace, or regenerate diseased tissues/organs in order to restore normal function. In this paper we will first discuss the general principle of regenerative medicine and the various techniques and approaches that have been used to replace or regenerate cells in diseased tissues and organs. Then, we will review different regenerative medicine approaches that have been used to treat specific diseased tissues and organs of the reproductive system in both animal and human experiments. It is clear from this article that regenerative medicine holds significant promise, and we hope that the review will serve as a platform for further development of regenerative medicine technologies for the treatment of inadequacies of the reproductive system., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Specific alterations in the pulsatility of luteinizing hormone (LH) are linked to obesity-related subfertility in ovulatory women. Vervet monkeys (Chlorocebus aethiops sabaeus) are an Old World nonhuman primate that develops obesity and has a menstrual cycle similar to humans. We evaluated follicular-phase LH pulses in 12 adult normal-weight female vervets. Serum was collected every 10 min for 4 h by using a tether device in conscious, freely moving monkeys on menstrual cycle days 2 through 5. Serum estradiol was collected daily during the follicular phase to identify the luteal-follicular transition. For comparison, we used data from 12 ovulatory normal-weight women who had undergone frequent blood sampling of early-follicular LH. LH pulse frequency was similar, with 2.8 ± 0.7 LH pulses during 4 h in vervets compared with 2.3 ± 0.7 LH pulses during 4 h in women. The LH pulse mass (percentage change in the pulse peak over the preceding nadir) was 123.2% ± 27.4% in vervets and 60.9% ± 14.9% in humans. The first day of low serum estradiol after the follicular-phase peak was denoted as the day of the luteal-follicular transition. Luteectomy was performed on luteal days 7 through 9, and corpora lutea were confirmed by histology. We demonstrate that follicular LH patterns in vervets are similar to those in humans and that the luteal phase is easily identified by monitoring daily serum estradiol. These findings demonstrate that vervet monkeys are a suitable animal model for evaluating LH pulse dynamics longitudinally in studies of diet-induced obesity.

Exposures to sex steroids during fetal development are thought to contribute to the unique urogenital anatomy and social dominance of the female spotted hyena: overt phenotypes not shared by other hyenids (i.e. striped hyena, brown hyena, and aardwolf). Because both androgens and estrogens influence development of genitalia and behavior, and because plasma SHBG regulates their access to tissues, we compared the Shbg gene sequences, structures, and steroid-binding properties in the four extant hyenids. We found the hyenid Shbg genes (>95% identical) and mature protein sequences (98% identical) are highly conserved. As in other mammals, the hyenid SHBG all bind 5α-dihydrotestosterone with high affinity (K(d) = 0.62-1.47 nm), but they also bind estrone and dehydroepiandrosterone with similarly high affinity, and this unusual property was attributed to specific amino acids within their SHBG steroid-binding sites. Phylogenetic comparisons also indicated that the spotted hyena SHBG precursor uniquely lacks two leucine residues and has a L15W substitution within its secretion signal polypeptide, the reduced size and hydrophobicity of which markedly decreases the production of SHBG and may therefore explain why serum SHBG concentrations in male and female spotted hyenas are approximately five times lower than in other hyenids. This is important because low plasma SHBG concentrations in spotted hyenas will increase exposure to biologically active androgens and estrogen as well as to their precursors (dehydroepiandrosterone and estrone), which may contribute to the masculinized external genitalia of female spotted hyenas and to female social dominance over males.

Objective: To describe the first case of monozygotic twin sisters with fragile X premutation and discordance for premature ovarian failure (POF)., Design: A descriptive case study., Setting: Academic center., Patient(s): Monozygotic twin sisters with fragile X premutation and discordance for POF., Intervention(s): Serum laboratory testing, fragile X premutation screening, zygosity testing, X-inactivation ratio and Southern blot studies., Main Outcome Measure(s): Incidence of POF in this twin cohort., Result(s): Zygosity analysis using polymerase chain reaction of 15 polymorphic markers via capillary gel electrophoresis in these patients confirmed their monozygosity. X-inactivation studies were performed using the human androgen receptor (HUMARA) gene and revealed similar X-inactivation ratios for both the patient and her sister (11:89 and 12:88, respectively) from peripheral serum samples. Southern blot evaluation of the proband and her sister revealed a similar methylation pattern in which the premutation allele was unmethylated much more than the normal allele. The contribution of the premutation on the active allele as determined by Southern blot analysis was consistent between sisters., Conclusion(s): The inactivation ratio studies and subsequent Southern blot analysis do not show differences between the patients; therefore, we are unable to identify a causative mechanism for the identical sisters' discordant phenotypes. It is possible that the inactivation ratios observed from the peripheral blood specimens obtained from the sisters do not represent the allele expression and skewing present at the level of the ovary., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To report our experience of conservative treatment in four patients with cervical ectopic pregnancy., Design: Case series., Setting: Academic medical center., Patients: Four women diagnosed with cervical ectopic pregnancy managed conservatively., Intervention(s): Systemic methotrexate alone or combined with subsequent uterine artery embolization (UAE)., Main Outcome Measures: Conservative management with decreased rate of serious complications., Results: No hysterectomies were needed. One patient required subsequent intervention, UAE., Conclusion: Conservative treatment of cervical pregnancy might be successful with careful follow up and subsequent conservative interventions.

Background: Symptomatic cesarean scar defect is one of the commonly reported long-term complications of cesarean section., Cases: We present two cases of symptomatic cesarean scar defect treated conservatively by robotic-assisted laparoscopy at our institution. Both patients presented with hematocele, pelvic discomfort and secondary infertility. Transvaginal ultrasound revealed hematocele measuring 3.7 x 1.9 x 3.8 cm and 3.0 x 2.0 x 1.6 cm in the lower uterine segments, respectively. After surgery normal menses resumed in both patients, and their childbearing potential was preserved. The patients conceived 3 and 11 months after surgery, respectively., Conclusion: Recognition of cesarean scar defect is important in the explanation of certain menstrual disorders since surgical intervention can result in improvement of symptoms and prevent the related secondary obstetric and gynecologic complications. Robotic-assisted laparoscopic approach is a good minimally invasive alternative for the repair of cesarean scar defect.

Objective: To describe a technique for frozen-banked ovarian tissue transplantation using robotic-assisted laparoscopy., Design: Case study., Setting: Academic tertiary care center., Patient(s): A 38-year-old patient in remission for non-Hodgkin lymphoma, whose ovarian tissue had been frozen for 3 years., Intervention(s): Robotic-assisted laparoscopic transplantation of thawed ovarian cortical tissue to the remaining ovary and peritoneum., Main Outcome Measure(s): Resumption of spontaneous menses, follicular development, and ovulation as demonstrated by ultrasound, and serum E(2) and P levels., Result(s): The patient experienced cyclic spontaneous menstruation 6 months after the transplantation. Ovulation was confirmed by ultrasound and serum E(2) and P levels at month 11 after surgery., Conclusion(s): Robotic-assisted laparoscopic surgery may be a good, minimally invasive alternative for the ovarian tissue transplantation procedure to restore ovarian function., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Severe postovum retrieval complications such as tuboovarian abscess are rare. We present an early pelvic infection case following egg retrieval., Case: A 31-year-old woman with unexplained infertility developed early pelvic infection subsequent to transvaginal oocyte retrieval (TVOR). Broad spectrum antibiotics were administered. Upon persistence of fever and ultrasonographic appearance of probable abscess, transvaginal ultrasound-guided drainage was performed on post-TVOR day 9 as well as posterior colpotomy and T-drain replacement into the cul de sac. Signs and symptoms of pelvic infection improved following drain replacement. Her beta-hCG was found to be positive in the following days. Drain was removed after 3 weeks. Her pregnancy follow-up was uncomplicated. She delivered a healthy baby vaginally at 38 gestational weeks., Conclusion: Early diagnosis with prompt administration of antibiotics and drainage may prevent poor pregnancy outcome in ovarian abscess patients subsequent to transvaginal oocyte retrieval.

Objective: To describe an early small bowel obstruction after robotic-assisted laparoscopic myomectomy with the Davinci system., Design: Case report., Setting: Academic medical center., Patient(s): Two days after a robotic-assisted laparoscopic myomectomy, a 35-year-old nulligravid African-American woman developed a small bowel obstruction due to retained myoma fragments that had implanted on and subsequently kinked loops of the small bowel., Intervention(s): The patient was managed conservatively for 4 days with bowel rest and IV hydration. Due to worsening clinical symptoms and supportive radiologic findings, exploratory laparotomy was performed to lyse adhesions and remove the implanted myoma pieces., Main Outcome Measure(s): Clinical resolution of small bowel obstruction symptoms., Result(s): No bowel resection was needed for this patient., Conclusion(s): Prompt recognition and operative treatment of the small bowel obstruction prevented the need for intestinal resection. To reduce the risk of ectopic implantation of myoma fragments, meticulous care should be taken to remove all remnants of morcellated tissue. Immediate postoperative complications, such as bowel obstruction, and long-term complications related to recurrent myomas may then be avoided., (Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

To evaluate if Chlamydia trachomatis IgG serology combined with hysterosalpingography can make it easier to detect tuboperitoneal factor infertility, we conducted a chart review of 76 consecutive patients at an infertility practice at West Virginia University from 1999-2001. We checked the charts for results of Chlamydia trachomatis IgG serology, Hysterosalpingography (HSG) and laparoscopy. Results of these tests were reviewed along with age, parity, previous reproductive tract disease surgery and duration of infertility. Complete data was found on 32 of the 76 patients. Chlamydia serology in conjunction with the HSG had a sensitivity of 80% for tuboperitoneal factor (tubal obstruction or pelvic adhesions), and a specificity of 82.3%. The positive predictive value was 80% and the negative predictive value was 82%. Since Chlamdia trachomatis IgG serologic testing is non-invasive and relatively inexpensive, we recommend combining it with hysterosalpingography as an infertility work-up. More invasive testing such as laparoscopy may be postponed or completely eliminated.

Objective: To determine if tubal rupture rates are decreased when a strict diagnostic algorithm is employed in the evaluation of women with suspected ectopic pregnancy as compared to individualized diagnostic methods., Study Design: Between 1994 and 1996, a group of investigators at Charleston Area Medical Center employed a strict diagnostic algorithm consisting of serum quantitative human chorionic gonadotropin (hCG) levels, progesterone levels, ultrasound and endometrial curettage in order to expedite diagnosis when ectopic pregnancy was suspected (group A patients). Other practitioners employed traditional criteria in similar clinical situations (group B patients). Medical records of patients diagnosed with ectopic pregnancy in this period were retrospectively reviewed. Demographic data, clinical and laboratory characteristics, and rate of tubal rupture were compared., Results: Sixty-one of 122 patients were diagnosed with ectopic pregnancy by strict criteria. These patients did not differ significantly from those evaluated by an individualized approach in regard to age, gravidity, parity or risk factors for ectopic pregnancy. Menstrual age, hCG levels and progesterone levels were similar as well. Group A patients had a median diagnostic interval of 2 days, with a range of 0-16. Group B patients had a median diagnostic interval of 8 days, with a range of 0-44 (P < .001). Of patients evaluated by this strict algorithm, 3.3% experienced rupture as compared to 23% of patients in group B (P < .001)., Conclusion: Use of a strict diagnostic algorithm in the evaluation of patients with suspected ectopic pregnancy resulted in decreased tubal rupture rates. Such an algorithm could be disseminated to all locations for triage of patients and use in a standardized manner. This practice could result in a reduction in loss of reproductive function and mortality secondary to ectopic pregnancy.

This preliminary report reviews our experience with 18 infertile patients with clomiphene-resistant polycystic ovary syndrome (PCOS). In the first treatment cycle, troglitazone was administered alone. During cycles 2-5, clomiphene was added with increments of 50 mg (up to 200 mg/day) if the previous cycle was anovulatory. Basal body temperature charts and serum progesterone were obtained to confirm ovulation. In a total of 66 treatment cycles, ovulation occurred in 44 (67%) and pregnancy in seven (11%). There were no significant changes in body weight, waist:hip ratio or liver enzymes during treatment. Troglitazone, alone or with clomiphene, induced ovulation in 15 of 18 patients (83%) and seven (39%) of them achieved pregnancy. This is the first report on ovulatory rates in clomiphene-resistant women with PCOS when troglitazone was used alone or with clomiphene. Recently, metformin and clomiphene were successfully used in women with PCOS. However, our patients represent a more resistant population of women with PCOS, with each patient serving as her own historical control by previous resistance to clomiphene. Although the pregnancy rate (39%) was promising for clomiphene-resistant women with polycystic ovary syndrome, it does not seem to have a definite advantage over gonadotrophins.

Female spotted hyenas exhibit male-like genitalia and dominance over males. Hyena ovarian tissues incubated in vitro produced large quantities of the steroid hormone precursor androstenedione. The activity of aromatase, which converts androstenedione to estrogen, was one-twentieth as great in hyena versus human placental homogenates. In comparison, the activity of 17 beta-hydroxysteroid dehydrogenase, which converts androstenedione to testosterone, was equal in the two homogenates. The limited aromatase activity may allow the hyena placenta to convert high circulating concentrations of androstenedione to testosterone, which results in virilization of the fetal external genitalia and possibly destruction of fetal ovarian follicles. Androstenedione production by residual ovarian stromal cells during reproductive life accounts for the epigenetic transmission of virilization in female spotted hyenas.

Concentrations of androgens (androstenedione, testosterone, 5 alpha-dihydrotestosterone), oestrogen and progesterone were measured in relation to pregnancy in the spotted hyaena (Crocuta crocuta). The gestation period was estimated to be about 110 days. There was a marked progressive rise in all the steroids starting in the first third of gestation. Chromatographic separation of plasma showed that much of the oestrogen is not oestradiol (only 12% of total measured) and that a significant fraction of the 'testosterone' may be dihydrotestosterone. In the final third of pregnancy, concentrations of androgen (especially testosterone plus dihydrotestosterone) in the female circulation reached the maximal values of adult males; the percentage of dihydrotestosterone relative to total testosterone plus dihydrotestosterone was higher in females (44 +/- 3.9%, n = 20) than in males (29.5 +/- 3.5%, n = 17). Plasma androstenedione was also significantly higher in females, but the increment was less than for oestrogen, testosterone and progesterone, and the temporal pattern was less clear. Samples from the maternal uterine and ovarian circulation showed that androstenedione is largely of ovarian origin and metabolized by the placenta, while testosterone, progesterone and oestrogen are primarily of placental or uterine origin. Fetal samples were taken from two mixed-sex sets of twins and one male singleton. Gradients across the placenta measured in the fetal circulation confirmed that the placenta metabolizes androstenedione and is a source of testosterone for the female fetus; there were no consistent differences in androgens between male and female fetuses. It is suggested that the conspicuous masculinization of the female spotted hyaena, especially evident in the external genitalia at birth, is a result, at least in part, of high placental production of testosterone or dihydrotestosterone derived from the metabolism of high maternal androstenedione.

The rat prostate consists of a series of branched ducts that eminate from the urethra. Heterogeneity of rat prostatic growth, secretory activity, and cell turnover has been observed along the proximal-distal axis of the branched ductal network. In addition, there are regional differences in androgen sensitivity along the ducts, with the distal ductal tips being highly androgen dependent and the proximal regions being relatively androgen independent. To determine the underlying mechanisms that may regulate these regional differences in androgen responsiveness, androgen receptor (AR) levels and 5 alpha-reductase activity were examined along the proximal-distal axis of microdissected ventral prostatic ducts from 15-, 30-, and 100-day-old rats. As in the murine prostate, DNA synthetic activity was concentrated in the distal tip region of the 15- and 30-day ducts. Immunocytochemistry and autoradiography with [3H] dihydrotestosterone were used to examine AR expression and functional ability to bind ligand, respectively. The results revealed no discernable differences in AR levels or binding activity in any cell type along the ductal length in prepubertal, pubertal, or adult rats. In addition, 5 alpha-reductase activity was the same in the distal and proximal ductal regions. We conclude that regional heterogeneity in prostatic growth and function is not a result of differences in levels of AR and 5 alpha-reductase. Rather, other region-specific structural, intracellular, or paracrine factors may be responsible for the differences in androgen responsiveness along the prostatic duct.