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STUDY OBJECTIVE: Compare the difference in postoperative morbidity for benign total hysterectomy by indication. DESIGN: Retrospective cohort. SETTING: United States hospitals participating in the American College of Surgeons National Surgical Quality Improvement Project database from 2018 to 2019. PATIENTS: Patients undergoing total hysterectomy for benign indications age 18 to 55 years old. INTERVENTIONS: Univariate comparisons were made between patients with hysterectomies for endometriosis and other benign indications. Unadjusted and adjusted logistic regression models were used to investigate the association between primary outcomes and hysterectomy indication; covariates in the adjusted model include age, race, ethnicity, and route. MEASUREMENTS AND MAIN RESULTS: A total of 29 742 women underwent hysterectomies, of which 3596 (12.1%) were performed for endometriosis. Patients undergoing hysterectomy for endometriosis were likely to be younger, were predominately White, and had less comorbidities. They were also more likely to have previous abdominal surgery, have previous pelvic surgery, undergo a laparoscopic approach, and undergo lysis of adhesions (all p <.001). Overall length of stay (≥1 day 73.1% vs 78.6%; p = .983) and operative time (median 118.0 vs 125.0 minutes; p <.001) were similar in both groups. Examining primary outcomes, patients with endometriosis were more likely to experience major morbidity (3.8% vs 3.4%; adjusted odds ratio [OR], 1.25; p = .033), with no difference in minor or overall morbidity (5.8% vs 6.9% [p = .874] and 8.8% vs 9.4% [p = .185], respectively). There were two 30-day mortalities, none in the endometriosis group. Patients with endometriosis were more likely to develop deep surgical site infection (SSI)/organ-space infection (2.3% vs 1.6%; OR, 1.42; p = .024) and less likely to receive blood transfusion (1.8% vs 3.0%; OR, 0.58; p <.001). There was no difference in occurrence of superficial SSI, sepsis, venous thromboembolism, readmission, or reoperation between groups. CONCLUSION: Patients undergoing hysterectomy for endometriosis were more likely to experience major morbidity and deep SSI, although overall major morbidity is rare.

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PURPOSE: The aim of this study was to determine if pregnancy-associated plasma protein-A (PAPP-A), typically measured in maternal serum and a potential predictor of adverse maternal and fetal outcomes such as spontaneous miscarriage, pre-eclampsia, and stillbirth, is expressed in blastocoel fluid-conditioned media (BFCM) at the embryonic blastocyst stage. DESIGN: This is an in vitro study. METHODS: BFCM samples from trophectoderm-tested euploid blastocysts (n = 80) from in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) patients were analyzed for PAPP-A mRNA. BFCM was obtained from blastocyst stage embryos in 20 uL drops. Blastocysts underwent trophectoderm biopsy for preimplantation genetic testing for aneuploidy prior to blastocyst vitrification and BFCM collection for snap freezing. cfDNA was synthesized using BFCM collected from 80 individual euploid blastocysts. Next, real-time qPCR was performed to detect expression of PAPP-A with GAPDH for normalization of expression in each sample. RESULTS: PAPP-A mRNA was detected in 45 of 80 BFCM samples (56.3%), with varying levels of expression across samples. CONCLUSION: Our study demonstrates the expression of PAPP-A in BFCM. To our knowledge, this is the first study to report detection of PAPP-A mRNA in BFCM. Further studies are required and underway to investigate a greater number of BFCM samples as well as the possible correlation of PAPP-A expression with pregnancy outcomes of transferred euploid blastocysts. If found to predict IVF and obstetric outcomes, PAPP-A may provide additional information along with embryonic euploidy for the selection of the optimal blastocyst for embryo transfer.

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OBJECTIVE(S): To determine if hysteroscopic removal of endometrial polyps, specifically via morcellation of polyps, affects implantation rate (IR), clinical pregnancy rate (CPR), spontaneous abortion (SAB) rate, and live birth rate (LBR) in first frozen embryo transfer (FET) cycles. STUDY DESIGN: Retrospective chart review, with data abstracted from the charts of all first autologous oocyte frozen embryo transfer (FET) cases (n = 135) at a single fertility center from January 2018 through June 2020. Subjects were grouped into (A) hysteroscopic polypectomy prior to first FET (n = 25) or (B) no hysteroscopic polypectomy prior to first FET (n = 110). The primary outcome was live birth rate (LBR). Secondary outcomes were implantation rate (IR), clinical pregnancy rate (CPR), and spontaneous abortion (SAB) rate. RESULTS: We found no difference between the groups in terms of the primary outcome (LBR) or the secondary outcomes IR, CPR, and SAB rate. CONCLUSION(S): The data analyzed here suggest that hysteroscopic morcellation of endometrial polyps has no adverse effect on IR, SAB rate, CPR, or LBR among first FET cases after this type of polypectomy.

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PURPOSE: The purpose of this study is to assess a potential association between FSH levels and testicular volumes with the severity of testicular histopathology on testicular biopsy in men with non-obstructive azoospermia (NOA) undergoing microdissection testicular sperm extraction (microTESE). METHODS: A retrospective chart review was performed from the electronic health records of men who underwent microTESE with NOA. RESULTS: Eighty-six men with NOA underwent microTESE with concomitant testicular biopsy for permanent section to assess the testicular cellular architecture. The histopathological patterns were categorized by severity indicating the odds of sperm retrieval into 2 categories. The unfavorable category included Sertoli cell only pattern and early maturation arrest (n = 50) and the favorable category included late maturation arrest and hypospermatogenesis patterns (n = 36). In the men with unfavorable histopathologic patterns, the mean FSH level was 22.9 ± 16.6 IU/L, and the mean testicular volume was 10.4 ± 6.0 cc. This was in comparison to men with favorable histopathologic patterns revealing a mean FSH level of FSH 13.3 ± 12.0 with a mean testicular volume of 13.3 ± 5.9 cc. There was a statistically significant higher FSH level in men with unfavorable histopathology than favorable (p = 0.004) as well as a significant smaller mean testicular volume in men with unfavorable histopathology (p = 0.029). CONCLUSIONS: Higher serum FSH levels and smaller testicular volumes are associated with more severe testicular histopathological patterns in men with NOA.

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Despite an estimated prevalence of 11% in women and plausible historical descriptions dating back to the 17th century, the etiology of endometriosis remains poorly understood. Classical theories of the histological origins of endometriosis are reviewed below. Clinical presentations are variable, and signs and symptoms do not correlate well with the extent of disease. In this summary, we have attempted to synthesize the growing evidence that hormonal and immune factors conspire to activate a local inflammatory microenvironment that encourages endometriosis to persist and elaborate mediators of its two cardinal symptoms: pain and infertility. Surprisingly, in the search for novel therapeutics for medical treatment of endometriosis, some compounds appear to have dual pharmacological functions, simultaneously modifying the endocrine and immune system facets of this complex gynecologic syndrome. We predict that these lead drugs will provide more therapeutic choices for patients in the future.

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OBJECTIVE(S): To determine if, among women with peritoneal endometriosis, the incidence of ovarian endometrioma at first laparoscopy differs between those with and without a history of hormonal contraceptive use. STUDY DESIGN: Retrospective case-control study of women who were patients at a fertility center and had first laparoscopy from 2009 through 2015 showing, at minimum, evidence of peritoneal endometriosis (n=136). Chart review was conducted for history of prior birth control use as well as operative and pathology notes of surgeries. Study subjects were grouped as follows: women with peritoneal endometriosis diagnosed by laparoscopy who had a history of hormonal contraceptive use (n=93) and women with peritoneal endometriosis diagnosed by laparoscopy who had never used hormonal contraceptives (n=43). The main outcome measure was the incidence of ovarian endometrioma among women with peritoneal endometriosis who had a history of hormonal contraceptive use as compared to women with peritoneal endometriosis who had a history of no hormonal contraceptive use. RESULTS: Among women with peritoneal endometriosis who had a history of hormonal contraceptive use, 17/93 (18.3%) were found to have endometriomas. Among women with peritoneal endometriosis who had a history of no hormonal contraceptive use, 21/43 (48.8%) were found to have endometriomas. The chi-square statistic was 13.6 (P-value<0.001). CONCLUSION(S): Among women with peritoneal endometriosis, those with a history of hormonal contraceptive use had a lower incidence of ovarian endometrioma than those with a history of no hormonal contraceptive use. Possible mechanisms of action include reducing the risk of a corpus luteum formation and subsequent transformation into an ovarian endometrioma or reducing the risk of ectopic endometrium implantation into the ovary via the diminution of retrograde menstruation. Although larger, prospective studies are needed, the findings of this study suggest that the use of hormonal contraception may decrease the likelihood of ovarian endometrioma formation among women with peritoneal endometriosis.

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PURPOSE OF REVIEW: Endometriosis is a common gynecologic condition estimated to affect 10-15% of reproductive-aged women, 30% of women with subfertility, and 80% of women with chronic pelvic pain. Although mainstays of diagnosis and treatment are still commonly applied, there have been various advances in the modalities of diagnosis and management of this complex condition. This article provides an updated review of novel findings regarding the diagnosis and management of this challenging disease. RECENT FINDINGS: Despite an abundance of studies on noninvasive diagnostic markers for endometriosis, there is no single imaging study, biomarker or panel of biomarkers that has been validated for clinical diagnosis. New technologies, such as use of indocyanine green and fluorescence, which visualize neovascularization often associated with endometriosis may improve diagnostic detection of endometriosis at the time surgery, but have not been demonstrated to improve pain outcomes after surgery. Hormone suppression remains the mainstay therapy prior to and following surgery. Although most methods demonstrate similar efficacy in reducing endometriosis-associated pain, newer pharmacologic agents that may prove advantageous include oral gonadotropin receptor antagonists, selective progesterone receptor modulators, and angiogenesis inhibitors. SUMMARY: Although there have been some advances in the study of noninvasive imaging and biomarkers, more investigation into effective modalities are being conducted and are needed.

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OBJECTIVE: To determine whether antimüllerian hormone (AMH) levels predict the availability of good-quality supernumerary blastocysts for cryopreservation. DESIGN: Retrospective study. SETTING: Two fertility centers. PATIENT(S): First fresh IVF cycles (n = 247) grouped as follows: 40 women <35 year old with AMH <1 ng/mL and 77 women with AMH 1-4 ng/mL; 62 women ≥35 year old with AMH <1 ng/mL, and 68 women with AMH 1-4 ng/mL. INTERVENTION(S): AMH level measured before IVF with ovarian stimulation protocols based on patient age and AMH level, including short gonadotropin-releasing hormone (GnRH) agonist, GnRH antagonist, or GnRH agonist microdose flare; supernumerary good-quality blastocysts cryopreserved on days 5 or 6 after retrieval. MAIN OUTCOME MEASURES(S): Supernumerary good-quality blastocysts for cryopreservation in relation to AMH levels. RESULT(S): Among women <35 years of age, there was a statistically significant difference in the number of patients with supernumerary good-quality blastocysts for cryopreservation between the groups with AMH <1 ng/mL and AMH 1-4 ng/mL (30.0% vs. 58.4%) when adjusted for age. Among women ≥35 years of age, there was a statistically significant difference in the number of patients with supernumerary good-quality blastocyst cryopreservation between groups with AMH <1 ng/mL and AMH 1-4 ng/mL (16.1% vs. 42.6%), when adjusted for age. CONCLUSION(S): Low AMH levels are associated with a statistically significantly lower likelihood of blastocysts for cryopreservation as compared with higher AMH levels. This effect was seen among women both <35 and ≥35 years of age. Patient counseling should include realistic expectations for the probability of good-quality supernumerary blastocysts available for cryopreservation.

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PURPOSE OF REVIEW: To take inventory of the past and present and project the future direction of our field to help train the next generation of providers. RECENT FINDINGS: Review the history of the subspecialty and factors contributing to its evolution. SUMMARY: Reproductive endocrinology and infertility's in-vitro fertilization future is shaping the intellectual priorities and surgical skill requirements of the next generation.

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INTRODUCTION: Fetal microchimerism has been implicated in the etiology of autoimmune diseases. This study was done to test the hypothesis that male fetal microchimerism is present in eutopic and ectopic endometrium (EM) obtained from women with endometriosis but not in eutopic EM from women without endometriosis. METHODS: A total of 31 patients were selected, including women with endometriosis (paired eutopic and ectopic EM; n = 19) and women without endometriosis (eutopic EM; n = 12). Tricolor interphase fluorescence in situ hybridization analysis was performed by cohybridization of CEP Y SpectrumAqua and CEP X SpectrumGreen (SG)/CEP Y SpectrumOrange probes. RESULTS: Ectopic EM from women with endometriosis had 75% XX chromosomes (double SG signals) and 25% X chromosomes (single SG signal). Y chromosomes were not observed in any of the eutopic/ectopic endometrial tissues from cases or controls. CONCLUSIONS: We were unable to confirm our hypothesis that male fetal microchimerism is present in eutopic and/or ectopic EM obtained from women with endometriosis.

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Endometriosis affects a significant proportion of reproductive-aged women. The impact of the disease on ovarian function is an important consideration when planning treatment in women who want to retain the potential of future childbearing. This review will specifically address the association between endometriomas and diminished ovarian reserve, with a particular focus on the impact of surgical endometrioma resection on ovarian function. The existing literature supports an adverse effect of ovarian endometriomas on spontaneous ovulation rates, markers of ovarian reserve, and response to ovarian stimulation, although data on clinical pregnancy and live birth rates remain inconsistent. Surgical removal of endometriomas may worsen ovarian function by removing healthy ovarian cortex or compromising blood flow to the ovary. It is evident that surgical excision of endometriomas acutely impairs ovarian function as measured by ovarian reserve markers; whether this represents progressive or long term impairment remains the subject of ongoing investigation.

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The da Vinci(®) robotic surgical system has been used more often in recent years for tubal anastomosis (TA) and has been reported to have an increased operative time. A one-stitch technique has been used for the reanastomosis step in laparoscopic TA. To date, publications on robotically-assisted TA (RATA) describe an anastomotic step with multiple (usually four) sutures placed. This retrospective case series reports tubal patency data on patients who underwent RATA with the one-stitch technique; tubal patency was the outcome measure. Eighteen women (ages 27-39) underwent RATA with the one-stitch anastomotic technique in tertiary care medical centers between February 2009 and May 2012. Tubal patency was demonstrated in 16/17 patients (94.1 %), as evidenced by postoperative hysterosalpingogram (HSG) and/or subsequent pregnancies. We report the first case series which shows that RATA with a single stitch for the reanastomotic step is effective in achieving tubal patency as evidenced by postoperative HSG and/or pregnancies.

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Endometriosis is a chronic disease in which epithelial and stromal cells that resemble the eutopic endometrium are found in ectopic lesions. In order to examine how microenvironmental factors such as extracellular matrix and macrophages influence disease progression, 12Z (an immortalized ectopic epithelial cell line) were cultured on tissue culture plastic (TCP) or in gels of recombinant basement membrane (rBM) or collagen I. Unlike cells in other conditions, cells in rBM formed multi-cellular structures in a 67 kDa non-integrin laminin receptor (67LR)-dependent manner. To examine the impact of macrophage-secreted factors on cell behavior, 12Z cells on all three substrates were treated with conditioned media from differentiated THP-1 (an immortalized monocytic cell line). Significant proliferation and invasion was observed only with cells cultured in rBM, indicating that extracellular matrix cues help dictate cell response to soluble signals. Cells cultured on rBM were then treated with individual cytokines detected in the conditioned media, with increased proliferation observed following exposure to interleukin-8 (CXCL8/IL-8) and both increased proliferation and invasion following treatment with heparin-binding EGF-like growth factor (HB-EGF). This study suggests that rBM gels can be used to induce in vitro lesion formation in order to identify soluble factors that influence proliferation and invasion.

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Endometriosis is a chronic inflammatory disease of reproductive age women leading to chronic pelvic pain and infertility. Current antiestrogen therapies are temporizing measures, and endometriosis often recurs. Potential nonestrogenic or nonsteroidal targets are needed for treating endometriosis. Peroxisome proliferator-activated receptor (PPAR)γ, a nuclear receptor, is activated by thiazolidinediones (TZDs). In experimental endometriosis, TZDs inhibit growth of endometriosis. Clinical data suggest potential use of TZDs for treating pain and fertility concurrently in endometriosis patients. Study objectives were to 1) determine the effects of PPARγ action on growth and survival of human endometriotic epithelial and stromal cells and 2) identify the underlying molecular links between PPARγ activation and cell cycle regulation, apoptosis, estrogen biosynthesis, and prostaglandin E2 biosynthesis and signaling in human endometriotic epithelial and stromal cells. Results indicate that activation of PPARγ by TZD ciglitazone 1) inhibits growth of endometriotic epithelial cells 12Z up to 35% and growth of endometriotic stromal cells 22B up to 70% through altered cell cycle regulation and intrinsic apoptosis, 2) decreases expression of PGE2 receptors (EP)2 and EP4 mRNAs in 12Z and 22B cells, and 3) inhibits expression and function of P450 aromatase mRNA and protein and estrone production in 12Z and 22B cells through EP2 and EP4 in a stromal-epithelial cell-specific manner. Collectively, these results indicate that PGE2 receptors EP2 and EP4 mediate actions of PPARγ by incorporating multiple cell signaling pathways. Activation of PPARγ combined with inhibition of EP2 and EP4 may emerge as novel nonsteroidal therapeutic targets for endometriosis-associated pain and infertility, if clinically proven safe and efficacious.

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The endometrium is ground zero when it comes to understanding how implantation occurs and how it might also fail, resulting in infertility or pregnancy loss. Many of the causes of diminished uterine receptivity are acquired during a woman's lifetime. Endometriosis, a major inflammatory disease affecting women, is also a leading cause of infertility and miscarriage. Once established, the inflammatory changes can, in some women, lead to progesterone resistance and downstream changes in endometrial gene expression. Much is now known about how inflammation translates to progesterone resistance and infertility, but much remains to be learned. In this review we provide an overview for understanding how the endometrium becomes dysfunctional, what biomarkers may hold promise for the diagnosis of endometriosis, and how progesterone resistance leads to infertility. Understanding the pathophysiology of this disease will likely lead to better treatment options.

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Endometriosis is a relatively common chronic gynecologic disorder that usually presents with chronic pelvic pain or infertility. The societal effect of this disorder is enormous both in monetary costs and in quality of life. The diagnosis of the disease can only be definitively made with surgical intervention. Fertility may be enhanced with surgical intervention, but medical suppressive therapy has no role apart from in vitro fertilization. Assisted reproductive technology is associated with excellent outcomes. Management of endometriomas is particularly complex because surgical intervention may reduce ovarian reserve. Both medical and surgical treatment of endometriosis-associated chronic pelvic pain are effective in the short-term. Recurrence is common with both modalities. Recurrence after surgical intervention can be decreased with the use of postoperative suppressive medical therapy such as hormonal contraceptives. This article presents the different types of peritoneal disease found in endometriosis patients. The technique used to safely and completely remove the disease is discussed. The specific areas of involvement include the pelvic side wall, the cul-de-sac, and bladder peritoneum.

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OBJECTIVE: To examine the impact of a recent surgery on development of endometriosis-related adhesions in a chimeric model and to determine the therapeutic efficacy of pioglitazone (PIO). DESIGN: Human endometrial biopsies were maintained in E(2) with or without PIO for 24 h before intraperitoneal injection into immunocompromised mice also treated with or without PIO at multiple time points after peritoneal surgery. The presence and extent of adhesions were examined in animals relative to the initial establishment of experimental endometriosis. SETTING: Medical school research center. PATIENT(S): Endometrial biopsies for experimental studies were provided by normally cycling women without a medical history indicative of endometriosis or adhesions. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Examination of the development of endometriosis-related adhesions in an experimental model. RESULT(S): Without therapeutic intervention, injection of E(2)-treated human endometrial tissue into mice near the time of peritoneal surgery resulted in multiple adhesions and extensive endometriotic-like disease. In contrast, PIO treatment reduced adhesive disease and experimental endometriosis related to surgical injury. CONCLUSION(S): The presence of human endometrial tissue fragments in the peritoneal cavity of mice with a recent surgical injury promoted development of both adhesive disease and experimental endometriosis. Targeting inflammation and angiogenesis with PIO therapy limited the development of postsurgical adhesions associated with ectopic endometrial growth.

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OBJECTIVE: Many women with endometriosis experience significant delay between the onset of symptoms and definitive diagnosis. Much is published on physician awareness of endometriosis and on the experiences of women with the condition. There is a paucity of data, however, surrounding perceptions of endometriosis in the general population. This study aims to assess knowledge of endometriosis among individuals of both genders. DESIGN: Survey study. SETTING: Family waiting room of a large university hospital. POPULATION: A total of 543 men and women. METHODS: Surveys were distributed to men and women over the age of 18 in the family waiting room of a large university hospital. MAIN OUTCOME MEASURES: A series of questions regarding the etiology, symptoms, and treatments for endometriosis were combined into a composite knowledge score. RESULTS: Knowledge of endometriosis was positively correlated with female gender, education level, regular health care, and exposure to individuals with the disease. Women diagnosed with endometriosis were more likely to have discussed symptoms of the condition with their physicians than women without the diagnosis. CONCLUSIONS: Individuals of both genders have limited knowledge of the signs and symptoms of endometriosis, which may contribute to the delay in diagnosis of the condition.

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