Salpingotomy versus salpingectomy in women with tubal pregnancy (ESEP study): an open-label, multicentre, randomised controlled trial.

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.

Gap junction blockade induces apoptosis in human endometrial stromal cells.

One of the most dynamic adult human tissues is the endometrium. Through coordinated, cyclical proliferation, differentiation, leukocyte recruitment, apoptosis, and desquamation, the uterine lining is expanded and shed monthly, unless pregnancy is established. Errors in these steps potentially cause endometrial dysfunction, abnormal uterine bleeding, failed embryonic implantation, infertility, or endometrial carcinoma. Our prior studies showed that gap junctions comprised of Gap junction alpha-1 (GJA1) protein, also known as connexin 43 (CX43), subunits are critical to endometrial stromal cell differentiation. The current studies were undertaken to explore the mechanism of endometrial dysfunction when gap junction intercellular communication (GJIC) is disrupted. Gap junction blockade by two distinct GJIC inhibitors, 18α-glycyrrhetinic acid (AGA) and octanol (OcOH), suppressed proliferation and induced apoptosis in endometrial stromal cells, as manifested by reduced biomarkers of cell viability, increased TUNEL staining, caspase-3 activation, sub-G1 chromosomal DNA complement, as well as shortened telomere length. Unexpectedly, we also observed that the chemical inhibitors blocked CX43 gene expression. Moreover, when endometrial stromal cells were induced to undergo hormonal decidualization, following a 7-day exposure to 10 nM 17ß-estradiol + 100 nM progesterone + 0.5 mM dibutyryl cAMP, characteristic epithelioid changes in cell shape and secretion of prolactin were blunted in the presence of AGA or OcOH, recapitulating effects of RNA interference of CX43. Our findings indicate that endometrial stromal cell proliferation and maintenance of decidualized endometrial function are GJIC-dependent, and that disruption of gap junctions induces endometrial stromal cell apoptosis. These observations may have important implications for several common clinical endometrial pathologies.

Improved Screening for Depression in Patients Initiating Fertility Treatment.

OBJECTIVE: To improve screening for depression in patients who are initiating fertility treatment at a reproductive endocrinology and infertility (REI) center by screening all patients at their initial visit using the Patient Health Questionnaire-9 (PHQ-9). DESIGN: This quality improvement project was conducted using a plan-do-study-act cycle implemented with a postintervention study design. SETTING/LOCAL PROBLEM: A medium-size REI center in a mid-Atlantic U.S. metropolitan area where screening for mental health status in patients initiating fertility treatments was not occurring. PARTICIPANTS: Patients who were scheduled in person with REI providers for a new patient consult regarding fertility were declared eligible. INTERVENTION/MEASUREMENTS: The PHQ-9 was administered by providers at initial consults for patients seeking fertility treatments from October 2022 to February 2023. Three cycles of the plan-do-study-act model were used to execute change. For all patients who scored 5 to 9 (mild depression), conversations regarding counseling referrals occurred. For all patients who scored ≥10 (moderate to severe depression), a referral for counseling and medication management was generated. Data were analyzed via descriptive statistics. RESULTS: A total of 115 participants were included. A screening rate of 84.3% (n = 97) was achieved for patients initiating treatment. Of the 97 screened, 21 patients had a score of ≥5; 19 were given a referral for counseling. However, none of the patients attended a counseling session or started medication prescribed by their primary care provider during the 2-month follow-up period. Barriers identified included costs, personal preferences, and access to services. CONCLUSION: The PHQ-9 screening tool was implemented at an REI clinic to improve the frequency of mental health screenings and provide necessary referrals. However, additional follow-up is needed to ensure patients are receiving appropriate mental health care.

Term delivery following transvaginal drainage of bilateral ovarian abscesses after oocyte retrieval: a case report.

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.

Robotic-assisted laparoscopic repair of symptomatic cesarean scar defect: a report of two cases.

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.

Successful conservative management of cervical ectopic pregnancy: a case series.

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.

Culdocentesis followed by saline solution-enhanced ultrasonography: technique for evaluation of suspected ectopic pregnancy.

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.

The ESEP study: salpingostomy versus salpingectomy for tubal ectopic pregnancy; the impact on future fertility: a randomised controlled trial.

BACKGROUND: For most tubal ectopic pregnancies (EP) surgery is the treatment of first choice. Whether surgical treatment should be performed conservatively (salpingostomy) or radically (salpingectomy) in women wishing to preserve their reproductive capacity, is subject to debate. Salpingostomy preserves the tube, but bears the risks of both persistent trophoblast and repeat ipsilateral tubal EP. Salpingectomy, avoids these risks, but leaves only one tube for reproductive capacity. This study aims to reveal the trade-off between both surgical options: whether the potential advantage of salpingostomy, i.e. a better fertility prognosis as compared to salpingectomy, outweighs the potential disadvantages, i.e. persistent trophoblast and an increased risk for a repeat EP. METHODS/DESIGN: International multi centre randomised controlled trial comparing salpingostomy versus salpingectomy in women with a tubal EP without contra lateral tubal pathology. Hemodynamically stable women with a presumptive diagnosis of tubal EP, scheduled for surgery, are eligible for inclusion. Patients pregnant after in vitro fertilisation (IVF) and/or known documented tubal pathology are excluded. At surgery, a tubal EP must be confirmed. Only women with a tubal EP amenable to both interventions and a healthy contra lateral tube are included. Salpingostomy and salpingectomy are performed according to standard procedures of participating hospitals. Up to 36 months after surgery, women will be contacted to assess their fertility status at six months intervals starting form the day of the operation. The primary outcome measure is the occurrence of spontaneous viable intra uterine pregnancy. Secondary outcome measures are persistent trophoblast, repeat EP, all pregnancies including those resulting from IVF and financial costs. The analysis will be performed according to the intention to treat principle. A cost-effectiveness analysis will be performed within a decision analysis framework, based on costs per live birth, including IVF treatment whenever a spontaneous pregnancy does not occur. Patients' preferences will be assessed using a discrete choice experiment. DISCUSSION: This trial will provide evidence on the trade off between salpingostomy and salpingectomy for tubal EP in view of the pros and cons of both interventions and will offer guidance to clinicians in making the right treatment choice. TRIAL REGISTRATION: Current Controlled Trials ISRCTN37002267.

Hysterectomy compared with endometrial ablation for dysfunctional uterine bleeding: a randomized controlled trial.

OBJECTIVE: To compare the effectiveness of hysterectomy and endometrial ablation in women with dysfunctional uterine bleeding. METHODS: The Surgical Treatments Outcomes Project for Dysfunctional Uterine Bleeding was a multicenter, randomized controlled trial. Eligible women were premenopausal with dysfunctional uterine bleeding and aged 18 years or older. Primary outcomes were problems that led the woman to seek care solved, bleeding, pain, and fatigue at 12 months. Additional outcomes included quality of life, adverse events, reoperation, and others at 24 months and up to 5 years. RESULTS: We randomly assigned 237 women between January 1998 and June 2001. Follow-up ended in June 2003. We completed 24 months of follow-up on 114 of 123 women assigned to endometrial ablation and 111 of 114 assigned to hysterectomy. Approximately 85% of women were aged younger than 45 years; 76.4% classified themselves as white, 18.6% as African American, less than 1% as Asian, 4.6% as American Indian, and 8.4% as Hispanic (classification within more than one category possible). Both endometrial ablation and hysterectomy were effective at 24 months in solving the problem that led women to seek care (84.9% compared with 94.4%), and in relieving bleeding, pain, fatigue, and other symptoms, although hysterectomy was more effective for bleeding. By 48 months, 32 of the 110 women initially receiving endometrial ablation required reoperation. Adverse events were more frequent with hysterectomy. CONCLUSION: Both endometrial ablation and hysterectomy are effective treatments in women with dysfunctional uterine bleeding. Hysterectomy (as the index surgery) was associated with more adverse events and a substantial number of patients receiving endometrial ablation had reoperation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00114088 LEVEL OF EVIDENCE: I.

Utilizing Chlamydia trachomatis IgG serology with HSG to diagnose tuboperitoneal-factor infertility.

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.

Scientific principles of regenerative medicine and their application in the female reproductive system.

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.

Assessing the pulsatility of luteinizing hormone in female vervet monkeys (Chlorocebus aethiops sabaeus).

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.

Phylogenetic comparisons implicate sex hormone-binding globulin in "masculinization" of the female spotted hyena (Crocuta crocuta).

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.

Robotic-assisted laparoscopic ovarian tissue transplantation.

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.

The first case described: monozygotic twin sisters with the fragile X premutation but with a different phenotype for premature ovarian failure.

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.

Early postoperative small bowel obstruction after laparoscopic myomectomy.

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.