Shahryar K. Kavoussi

Periodontal disease and endometriosis: analysis of the National Health and Nutrition Examination Survey.

OBJECTIVE To investigate whether an association exists between endometriosis and periodontal disease, because endometriosis and periodontal disease are chronic, inflammatory processes more common in patients with systemic autoimmune disorders and because each disease alters immune modulators. DESIGN Cross-sectional study. SETTING University health system and statistical center. PATIENT(S) Data for 4136 women, ages 18-50, in the National Health and Nutrition Examination Survey, 1999-2004. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Periodontitis and gingivitis among those patients with and without self-reported endometriosis. RESULT(S) Multinomial logistic regression showed that women with self-reported endometriosis had significantly (57%) higher odds of having both gingivitis and periodontitis relative to not having periodontal disease, compared with women without self-reported endometriosis (adjusted odds ratio, 1.57; 95% confidence interval, 1.06, 2.33), when controlling for other relevant factors. CONCLUSION(S) The results of this study suggest a possible association between endometriosis and periodontal disease. Although it is conceivable that the multifactorial development of endometriosis may be augmented by an immune response to an infectious agent, the potential underlying link between endometriosis and periodontal disease may be a generalized, global immune dysregulation.

PPARγ Activation Inhibits Growth and Survival of Human Endometriotic Cells by Suppressing Estrogen Biosynthesis and PGE2 Signaling.

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.

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.

Cervical cancer screening with liquid cytology in women with developmental disabilities.

OBJECTIVE To evaluate the use of liquid cytology in Pap smears in women with developmental disabilities (DD) for endocervical cell yield and abnormalities, via speculum examination or blind technique. METHODS We used retrospective chart review of gynecological visits by women with DD from October 2002 to November 2005. Cervical cytology screening included speculum examination or blind technique. Endocervical cell yield was analyzed via Pearsons chi-square test. RESULTS Of 240 attempted liquid cytology Pap smears, 199 (82.9%) were completed. Of these, 193 met inclusion criteria for the study, and 120 (62.2%) contained endocervical cells. The endocervical cell yield with liquid cytology/speculum was 80.0% and was 43.6% with liquid cytology/blind (p < 0.001). Two blind smears (1.0%) were abnormal; both revealed atypical squamous cells of undetermined significance (ASCUS) with subsequent negative human papillomavirus (HPV) typing. CONCLUSIONS Cervical screening with liquid cytology in women with DD provides an overall rate of endocervical cells of approximately 44%-80% depending on the technique used. Although this is much lower than in the general population, this compares favorably with slide Pap smear in women with DD. The 44% yield of endocervical cells and the finding of abnormal Pap smears with the blind technique suggest this is a reasonable alternative for obtaining Pap smears in women with difficult pelvic examinations who otherwise would not receive cervical screening.

Thiazolidinediones decrease vascular endothelial growth factor (VEGF) production by human luteinized granulosa cells in vitro

OBJECTIVE To determine the effect of thiazolidenedione derivatives (TZDs) on vascular endothelial growth factor (VEGF) production by human luteinized granulosa cells and the morphologic development of murine embryos. DESIGN Prospective, experimental, in vitro and in vivo study. SETTING Research laboratory. PATIENT(S) Follicular aspirates from 10 women undergoing oocyte retrieval. INTERVENTION(S) Isolated human granulosa cells were treated with a dimethyl sulfoxide (DMSO) control or ciglitazone, in the presence and absence of an hCG stimulus. Embryos extracted from superovulated B6C3F1 female mice were cultured in the presence of DMSO or pioglitazone. MAIN OUTCOME MEASURE(S) Vascular endothelial growth factor concentrations at 24 and 48 hours. Morphologic development of murine embryos at 96 hours. RESULT(S) Following an hCG stimulus, treatment with 20 microM or 40 microM ciglitazone decreased VEGF production in a statistically significant manner at both time intervals. Blastocyst development at 96 hours did not significantly differ between untreated zygotes and those treated with pioglitazone. CONCLUSION(S) Ciglitazone significantly decreased VEGF production by human granulosa cells in an in vitro model. Pioglitazone did not adversely impact the development of cultured murine embryos. Although mechanistic evidence is not provided, the pivotal role of VEGF in ovarian hyperstimulation syndrome prompts investigation of TZDs as a novel treatment for this condition.

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.

Sperm retrieval and concomitant tumor resection in azoospermic men with congenital adrenal hyperplasia and bilateral testicular adrenal rest tumors: a case report

PurposeThe objective of this study was to offer a new treatment approach for sperm retrieval simultaneously with tumor resection in azoospermic men with congenital adrenal hyperplasia (CAH), orchialgia, and bilateral testicular adrenal rest tumors (TARTs) who fail to respond to medical treatment.MethodsThis is a retrospective chart review from a couple’s fertility center.ResultsBetween May 2013 and May 2015, two azoospermic men with CAH and bilateral TARTs, with orchialgia, and desire to conceive underwent bilateral TART resection in the same surgical setting as sperm retrieval after remaining azoospermic with normalization of gonadotropins with treatment with human chorionic gonadotropin (hCG). Both men had adequate sperm retrieved for in vitro fertilization/intracytoplasmic sperm retrieval (IVF/ICSI) at the time of bilateral TART resections. They had complete TART resections with resolution of orchialgia. The wife of one patient had a successful pregnancy with use of retrieved sperm resulting in a live birth, and the sperm from the other man is cryopreserved for future use.ConclusionsIt is feasible to perform successful sperm retrieval simultaneously with TART resection in azoospermic men with CAH after medical treatments with persistent azoospermia, rather than subjecting these men to multiple invasive procedures.

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.

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.

Investigational Medical Therapies for Endometriosis: Current Data and Future Trends

Abstract Current mainstays of medical therapy for endometriosis preclude fertility or may have unwanted side effects. Therefore, research has been underway to find alternatives to current options which may be applied to future medical treatment. The focus of this review is that of investigational hormonal and nonhormonal medical therapies based on in vitro and in vivo animal models of endometriosis as well as in human endometrial and endometriotic cells in vitro. Assessment of the safety and efficacy of such novel medical treatments have been, and continue to be, necessary prior to clinical trials.