Comparing Characteristics of and Postoperative Morbidity after Hysterectomy for Endometriosis versus other Benign Indications: A NSQIP Study.

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.

The expression of pregnancy-associated plasma protein-A (PAPP-A) in human blastocoel fluid-conditioned media: a proof of concept study.

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.

FSH levels and testicular volumes are associated with the severity of testicular histopathology in men with non-obstructive azoospermia.

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.

New paradigms in the diagnosis and management of endometriosis.

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.

Reproductive endocrinology and infertility fellowships: is the 'reproductive endocrinology' portion obsolete?

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.

Effect of surgery for endometrioma on ovarian function.

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.

The effects of hysteroscopic morcellation of endometrial polyps on frozen embryo transfer outcomes.

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.

Public perceptions of endometriosis: perspectives from both genders.

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.

Endometriosis-associated nerve fibers and pain.

The assessment and diagnosis of endometriosis remain elusive targets. Patient and medical-related factors add to delays in the detection and treatment. Recently, investigators have revealed specific nerve fibers present in endometriotic tissue, with existing parallels between density and pain severity. The aim of this review is to compile a comprehensive review of existing literature on endometriosis-related nerve fiber detection, and the effects of medical therapy on these neural fibers. We performed a systematic literature-based review using Medline and PubMed of nerve fibers detected in eutopic endometrium, endometriotic lesions, and the peritoneum. Various arrangements of significant medical terms and phrases consisting of endometriosis, pelvic pain, nerve fiber detection/density in endometriosis, and diagnoses methodology, including treatment and detection were applied in the search. Subsequent references used were cross-matched with existing sources to compile all additional similar reports. Similar nerve fibers were detected within lesions, endometrium, and myometrium, though at varying degrees of density. Hormonal therapy is widely used to treat endometriosis and was shown to be related to a reduction in fiber density. A direct result of specific nerve fiber detection within eutopic endometrial layers points to the use of a minimally invasive endometrial biopsy technique in reducing delay in diagnosis and subsequent possible preservation of fertility.

Thiazolidinediones as therapy for endometriosis: a case series.

BACKGROUND: Current medical therapies for endometriosis result in delayed conception and have not been shown to provide any fertile benefit subsequent to treatment. Thiazolidinediones (TZDs) do not impede conception and have been shown to reduce endometriotic lesions in animal models; however, no studies have been performed in humans. The aim of this study was to provide preliminary data about the effectiveness of a TZD in treating endometriosis-related pain. METHODS: Case series of women with endometriosis recruited from the University of Michigan as part of an open-label prospective phase 2a clinical trial. Participants were given rosiglitazone, 4 mg daily, for 6 months. Subjective endometriosis symptoms were assessed using a modified Biberoglu and Behrman symptom severity scale and the McGill pain questionnaire. RESULTS: Two of the 3 patients exhibited improvement in severity of symptoms and pain levels with a concurrent decrease in pain medication, while 1 experienced no change. Rosiglitazone was well tolerated by all patients. CONCLUSIONS: Combined with data gathered from studies in rats and nonhuman primates, the results from this study offer positive justification for using TZDs as a well-tolerated treatment for endometriosis that can address pain without impeding ovulation and without the need for add-back therapy.

Pathogenesis of endometriosis: Interaction between Endocrine and inflammatory pathways.

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.

Incidence of ovarian endometrioma among women with peritoneal endometriosis with and without a history of hormonal contraceptive use.

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.

Endometrioma complicated by tubo-ovarian abscess in a woman with bacterial vaginosis.

BACKGROUND: Tubo-ovarian abscess involvement of an endometrioma has been reported in cases of patients with polymicrobial sources such as Neisseria gonorrhoeae, Chlamydia trachomatis, and obligate anaerobic bacteria; however, bacterial vaginosis (BV) predisposing to abscess formation in an endometrioma has not been reported to date. CASE: Superinfection of an endometrioma was surgically diagnosed in a patient with known advanced-stage endometriosis after she presented with acute pelvic inflammatory disease symptoms and was unresponsive to antibiotic therapy. Gram-negative rods were cultured from the endometrioma. On admission, cervical, blood, and urine cultures were negative; BV was diagnosed on normal saline wet prep and gram stain. CONCLUSION: This case raises the possibility of BV ascension to the upper genital tract predisposing to abscess formation in endometriomas. Therefore, aggressive treatment of BV in patients with known advanced-stage endometriosis may be considered to prevent superinfected endometriomas.

Angiogenic effects of norplant contraception on endometrial histology and uterine bleeding.

Norplant, a sc contraceptive device, releases levonorgestrel in a sustained fashion. Its effectiveness is offset by irregular bleeding patterns. Because vascular endothelial growth factor (VEGF) is stimulated by synthetic progestogens in vitro and in vivo, we postulated that correlations between this angiogenic factor and uterine bleeding patterns might exist. Twenty-eight women who were exposed to Norplant and 13 control women were prospectively followed for 6-8 months. Bleeding diaries were collected, hysteroscopies were performed, endometrial biopsies were obtained for standardized histological evaluation, and VEGF histochemical immunostaining (H)-scores were assigned. Cluster determination-34 (CD34) staining was also performed to quantify the number of endometrial blood vessels per high-power field. Irregular uterine bleeding was common among women using Norplant devices. Endometrial VEGF H-scores were greater in women using Norplant than in control women. New findings of this study show that vessel density did not correlate with epithelial VEGF H-scores but was highly associated with the intensity of stromal and perivascular VEGF. VEGF expression in the latter regions correlated significantly with hysteroscopic abnormalities and irregular bleeding. The expression of this angiogenic protein, particularly in the stromal and perivascular compartments, correlated with microvascular density, hysteroscopically documented hypervascularity, and uterine bleeding profiles. Irregular bleeding with Norplant use appears to reflect paracrine-mediated effects on vascular function by angiogenic factors, such as VEGF.

Lack of Evidence That Male Fetal Microchimerism is Present in Endometriosis.

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.

Antimüllerian hormone as a predictor of good-quality supernumerary blastocyst cryopreservation among women with levels <1 ng/mL versus 1-4 ng/mL.

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.

Long-term progestin treatment inhibits RANTES (regulated on activation, normal T cell expressed and secreted) gene expression in human endometrial stromal cells.

RANTES (regulated on activation, normal T cell expressed and secreted) is synthesized by endometrial and endometriotic stromal cells and circulates in peritoneal fluid. Reports indicate that medroxyprogesterone acetate (MPA) is clinically effective in alleviating pelvic pain in the majority of endometriosis patients, which leads us to hypothesize that MPA may be antiinflammatory. Prolonged treatment (8 d) with MPA resulted in 36% and 50% decreases in luciferase activity and RANTES protein production, respectively, whereas shorter treatment (2 or 4 d) with MPA had no significant effect. We also observed that 8 d of MPA increased PR expression. Both effects were blocked by RU486. Cotransfection of endometrial stromal cells with PR enhanced the effects mediated by endogenous PR. In addition, its action via progesterone response element cis-elements, PR appeared to inhibit trans-activation of a nuclear factor-kappaB-responsive element, further suppressing RANTES expression. These studies indicate that prolonged progestin exposure down-regulates endometrial RANTES gene transcription in vitro. The effect is PR dependent and mediated in part through a nuclear factor-kappaB pathway. The clinical effectiveness of chronic progestin treatment in endometriosis-associated pelvic pain may be attributed to its inhibition of RANTES production and its suppression of inflammatory responses in the pelvis.

Peritoneal macrophages induce RANTES (regulated on activation, normal T cell expressed and secreted) chemokine gene transcription in endometrial stromal cells.

Peritoneal fluid macrophages (PFM) are activated in women with endometriosis, in whom they are thought to mediate or exacerbate inflammation. The effect of PFM on endometrial stromal cells (ESC) was studied using a coculture model to evaluate the influence of IL-1 beta and other macrophage-derived cytokines on the transcriptional activation of the human RANTES (regulated on activation, normal T cell expressed and secreted) gene. Normal endometrial biopsies from four patients were used to prepare stromal cell cultures, and pelvic fluid was collected to isolate peritoneal macrophages. A full length (-940 bp) human RANTES promoter construct provided an indicator of transcriptional activation in luciferase reporter transfection assays. Without lipopolysaccharide (LPS), cocultures with PFM had no effect on ESC RANTES gene expression. However, when PFM were treated with LPS within the coculture apparati, ESC RANTES promoter activity was increased more than 2-fold (P < 0.05). The addition of IL-1 receptor antagonist abrogated activation of the RANTES luciferase transgene by LPS-induced PFM products (P < 0.05). We identified IL-1 from PFM as a major stimulus to initiate ESC RANTES gene expression in cocultures. We postulate that PFM stimulation of RANTES production by ESC could lead to a self-propagating recruitment of inflammatory cells that contribute to the development and progression of endometriotic lesions.

Angiogenic factors in endometriosis.

Similar to tumor metastases, endometriotic implants require neovascularization to establish, grow, and invade. The peritoneal environment is ideally suited to provide a proangiogenic milieu. Nevertheless, endometriotic lesions are found only in a minority of reproductive-age women (approximately 10%) with retrograde menstruation. In this paper, we review the major cytokines, growth factors, steroid hormones, and eicosanoids responsible for angiogenesis in endometriosis. We postulate that interference with angiogenic principles expressed in the peritoneum may constitute novel therapeutic opportunities for the prevention, amelioration, or treatment of pelvic endometriosis.

Peroxisome proliferator-activated receptor-gamma induces regression of endometrial explants in a rat model of endometriosis.

OBJECTIVE: To determine the effects of a thiazolidinedione, ciglitazone, in a rat model of endometriosis. DESIGN: Prospective, randomized, placebo-controlled study. SETTING: Experimental surgery laboratory in a university department. ANIMAL(S): Twenty female Sprague-Dawley rats given endometriotic lesions by transplanting autologous uterine tissue to ectopic sites on the peritoneum. INTERVENTION(S): Four weeks after surgery, 20 rats were randomly divided into two groups and treated with IP injections of vehicle every other day (control; n = 10) or ciglitazone (1 mg per rat; n = 10) and euthanized 4 weeks from the start of treatment. MAIN OUTCOME MEASURE(S): At the end of treatment, laparotomy was performed to photograph each explant and then they were measured and weighed. Histologic analysis was performed on the uterine allograft, ovary, and eutopic uterine tissue. RESULT(S): By histologic assessment, both groups maintained folliculogenesis and normal eutopic endometrial architecture. Treatment with ciglitazone significantly decreased the size of ectopic uterine tissues and the mean explant wet weight. The ciglitazone-treated group showed marked epithelial regression compared with the control group. CONCLUSION(S): We conclude that a PPAR-gamma ligand, ciglitazone, reduced the size of experimental endometriosis in the rat model of endometriosis. This animal model suggests that a thiazolidinedione drug may be helpful in women with endometriosis.