The development of endometriosis in a murine model is dependent on the presence of dendritic cells.

Endometriosis is a common condition associated with pelvic pain and infertility. This study group has previously shown that supplementation of dendritic cells led to enhancement of endometriosis lesion growth and angiogenesis. This study determined whether endometriosis is dependent on the presence of endogenous dendritic cells. Surgical induction of endometriosis was performed in CD11c⁺ DTR/GFP transgenic (Tg) female mice in which dendritic cells were ablated upon injection of diphtheria toxin (DT). Mice were allocated into four groups (n=5 each): group I, wild-type mice treated with vehicle; group II, wild-type mice treated with DT; group III, Tg mice treated with DT; and group IV, Tg mice treated with vehicle. After 10 days, mice were killed and endometriosis lesions were analysed by flow cytometry. DT treatment led to ablation of dendritic cells in spleens and endometriosis lesions in Tg mice while no ablation was observed in controls. Corresponding to dendritic cell ablation, endometriosis lesions in group III were ∼5-fold smaller than in the control groups (ANOVA P<0.0001). This study suggests that endometriosis development is dependent on the presence of endogenous dendritic cells. Therapies designed to inhibit dendritic cell infiltration as possible treatments for endometriosis warrant further study.

Aberrant endocrinology and ovarian response to clomiphene citrate during the course of an undiagnosed early intrauterine pregnancy: a case report.

BACKGROUND: This is an unusual case of embryonic exposure to clomiphene citrate (CC) in the setting of an undiagnosed early pregnancy with successful follicular response to CC and progression of pregnancy despite markedly attenuated serum progesterone and estradiol levels and a thin endometrium. A review of literature on the potential of CC for teratogenicity is presented. CASE: A 36-year-old woman underwent 2 ovulation inductions (OIs) with CC. Successful pregnancy followed the second OI cycle. Fetal measurements on transvaginal ultrasound identified the pregnancy to be chronologically advanced and consistent with the first OI treatment cycle. The follicular response to CC during the second OI cycle in the setting of ongoing early pregnancy, and pregnancy progression despite markedly attenuated endometrium, low serum levels of serum progesterone, and estradiol and embryonic exposure to CC, are notable. CONCLUSION: The possibility of inadvertent embryonic exposure to fertility drugs in the event of undiagnosed early pregnancy must be considered in infertile patients pursuing repeat treatment cycles. Serum beta-hCG testing should be considered before repeat treatments.

Relevance of vitamin D in reproduction.

The steroid hormone vitamin D is historically recognized for its relevance to bone health and calcium homeostasis. Recent years have witnessed a shift in focus to non-skeletal benefits of vitamin D; in this latter context, an accruing body of literature attests to a relevance of vitamin D to reproductive physiology. This article reviews the existing data about the diverse and previously underappreciated roles for vitamin D in reproductive health. A large body of available literature suggests that vitamin D deficiency may be detrimental to reproductive biology. However, given that our appreciation of vitamin D's role in reproductive physiology is almost entirely shaped by 'associative' studies and that data based on prospective interventional trials are limited, these concepts remain predominantly conjectural. Exact mechanisms whereby vitamin D may participate in the regulation of reproductive physiology remain far from clear. This review underscores a need for appropriately designed intervention trials to address the existing knowledge gaps and to delineate the specific roles of vitamin D signaling in reproductive biology.

The impact of preconceptual diet on the outcome of reproductive treatments.

PURPOSE OF REVIEW: To discuss the dietary factors that influence the reproductive outcomes in patients undergoing fertility treatment. RECENT FINDINGS: Recent studies have found that a woman's nutritional status and dietary intake can play a role in her reproductive health. In addition to weight, specific dietary patterns rich in omega-3 fatty acids and micronutrients such as vitamin D have all been shown to impact fertility. Although data regarding diet and fertility treatment are limited with many studies lacking the statistical power to validate findings, recent studies corroborate the importance of a balanced diet and appropriate weight management program while undergoing fertility treatment. SUMMARY: The growing reliance on assisted reproductive technologies in conjunction with the increase in the general population's weight and poor nutritional status has raised questions as to the effects of dietary status and weight on fertility treatment outcome. A review of findings thus far indicates potential avenues for future research to further elucidate cytotoxic and genotoxic dietary factors as well as dietary elements that may improve oocyte quality, aid implantation, as well as pregnancy maintenance during the periconception period.

mTOR kinase inhibition results in oocyte loss characterized by empty follicles in human ovarian cortical strips cultured in vitro.

OBJECTIVE: To determine whether oocyte loss is induced by mTOR kinase inhibition in human cortical strips as seen in model organisms in vivo and in vitro. DESIGN: Ovarian cortex was collected at two centers and cut into small strips. Strips were cultured for 6 days with or without the mTOR inhibitor rapamycin (RAP; 100 nM). Strips were then embedded in paraffin, and serial sections were prepared. SETTING: Samples were collected in general obstetric (Edinburgh), gynecologic surgery (New Haven), and fertility preservation assisted reproductive technology (ART) (New Haven) practices. PATIENT(S): Ovarian cortex collected from patients (15-34 years of age) during cesarean section (donated tissue) was removed for the purposes of fertility preservation or was prepared after oophorectomy. INTERVENTION(S): Tissue was used for research purposes only, with no subsequent patient intervention. MAIN OUTCOME MEASURE(S): Follicles were counted and assessed in each serial section. Caspase activity was monitored to determine whether mTOR inhibition activated apoptosis. RESULT(S): The RAP inclusion in cultures results in significantly fewer follicles compared with ethanol vehicle-treated controls. Furthermore, RAP treatment resulted in the induction of follicles that lacked an oocyte in any serial section (30/161 follicles vs. 1/347 ethanol vehicle-treated follicles). Caspase activity was not elevated by RAP treatment. CONCLUSION(S): mTOR inhibition results in a conserved destruction of the oocyte by adjacent granulosa cells (GC) in the absence of increased caspase activity. This model of oocyte loss is not consistent with classic apoptosis/atresia.

Third party reproduction and the aging couple.

The average age of childbearing has been increasing in industrialized nations, including the United States. As a result, more women in their late 30s to early 40s are seeking their first pregnancy than ever before. Unfortunately, fertility declines with increasing female age. In addition, success of infertility treatments including those using assisted reproductive technologies (ART) decreases as the age of the female partner advances. Third party reproduction involves using gametes or the uterus of a third person to achieve pregnancy. Oocyte donation is a common form of third party reproduction, associated with significant success rates, which gives aging couples an opportunity to bear children. For safety and success, all the participants must be extensively screened medically and psychologically. In addition, a detailed understanding of the process by all parties involved should be achieved. While third party reproduction through oocyte donation is a long and labor intensive process with a significant amount of emotional, financial, and physical involvement from all parties, it is quite often a gratifying experience for everyone involved which include, oocyte donors, recipients, social workers, nurses and physicians.

Does the ovarian reserve decrease from repeated ovulation stimulations?

PURPOSE OF REVIEW: The majority of infertility patients require more than one in-vitro fertilization cycles to achieve pregnancy, which results in repeated stimulation in the ovaries. There have been raising concerns for patients about the effect of repetitive assisted reproductive technology (ART) cycles on ovarian response in subsequent cycles. Whether or not there is deterioration in ovarian response with repetitive treatment will allow clinicians to provide better counseling to patients before treatment. RECENT FINDINGS: The single determinant factor that has been shown in affecting ovarian reserve for patients undergoing repeated ART cycles is age. Current evidence has suggested that repetitive ovarian stimulation cycles with intrauterine insemination can be performed without clinically impairing ovarian response. Oocyte donors can be invited for at least three cycles without a negative effect on ovarian response to gonadotropins, number of mature oocytes retrieved, embryo quality, or pregnancy rates. SUMMARY: There are limited available published data on this topic. Research studies have shown that there is no detrimental effect on ovarian function of egg donors who undergo repetitive ovarian hyperstimulation. Overall findings also show that there is no significant decline in ovarian reserve in patients who undergo up to three repeated in-vitro fertilization cycles. For patients undertaking more than three cycles, the results become equivocal because age becomes a determinant factor with both pregnancy and live birth rate declining with repetitive cycles.

Regulation of monocyte chemotactic protein-1 expression in human endometrial endothelial cells by sex steroids: a potential mechanism for leukocyte recruitment in endometriosis.

The main aim of this study is to describe the in vivo temporal and spatial expression of monocyte chemotactic protein 1 (MCP-1) in human endometrial endothelial cells (HEECs) and to compare the in vitro regulation of MCP-1 expression by sex steroids in HEECs from women with or without endometriosis. Eutopic endometrial tissues and endometriosis implants were grouped according to the menstrual cycle phase and were examined by immunohistochemistry for MCP-1 expression. No significant difference was observed for MCP-1 immunoreactivity in the endothelial cells of eutopic endometrium of women with endometriosis when compared to endometrium of women without endometriosis and to endometriosis implants. For in vitro studies, the purity of cultured HEECs (90%-95%) was confirmed by immunocytochemistry using endothelium-specific markers CD31 and CD146. The effects of estradiol (5 x 10(- 8) mol/L), progesterone (10(-7) mol/L), or both on MCP-1 messenger RNA (mRNA) and protein levels were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and enzyme-linked immunosorbent serologic assay (ELISA), respectively. Sex steroids did not have significant effect on MCP-1 mRNA and protein expression in HEECs from women without endometriosis. However, we observed that the sex steroid treatment stimulated MCP-1 mRNA and protein expression in HEECs from women with endometriosis (P < .05). We postulate that the stimulation of chemokine expression by sex steroids in the endometrial endothelial cells in women with endometriosis may play a central role in recruiting mononuclear cells, therefore contributing to the inflammatory aspect of endometriosis.

Evaluation of compliance and range of fees among American Society for Reproductive Medicine-listed egg donor and surrogacy agencies.

OBJECTIVE: To evaluate the compliance of donor and surrogacy agencies to American Society for Reproductive Medicine (ASRM) guidelines and assess regional differences in agency, donor, and surrogacy fees in the United States. METHODS: A retrospective study was performed of websites from agencies that have signed an agreement with the Society for Reproductive Technology (SART) to abide by ASRM guidelines in governing egg donor prices and surrogacy compensation. RESULTS: A total of 66 agencies are listed on the website, divided into 8 national regions; 24.5% of egg donor agencies deviated from ASRM guidelines. There was no significant difference in the agency fees among the different regions of United States, but the agency fees for egg donation trend higher in the west. CONCLUSION: A substantial number of egg donor agencies in the United States are not abiding by the ASRM guidelines. Oversight may be needed to correct improper marketing practices for egg donor recruitment.

Intrauterine adhesions as a risk factor for failed first-trimester pregnancy termination.

BACKGROUND: Risk factors for failed first-trimester surgical abortion include endometrial distortion caused by leiomyomas, uterine anomalies and malposition and cervical stenosis. This report introduces intrauterine adhesions as an additional risk factor. CASE: A multiparous woman presented for pregnancy termination at 6 weeks' gestation. Three suction-curettage attempts failed to remove what appeared to be an intrauterine pregnancy. Rising beta-hCG levels and concern for an interstitial ectopic pregnancy prompted a diagnostic laparoscopy and exploratory laparotomy without the identification of an ectopic pregnancy. After methotrexate treatment failed, the patient underwent ultrasound-guided hysteroscopy and suction curettage using a cannula with a whistle-cut aperture for the successful removal of a pregnancy implanted behind intrauterine adhesions. CONCLUSION: Intrauterine adhesions are a cause of failed surgical abortion. Ultrasound-guided hysteroscopy may be required for diagnosis.

The superinfection of a dermoid cyst.

Mature cystic teratoma may be complicated by torsion, rupture, and malignant change, but is rarely complicated by infection. Here we report the case of a patient who presented with a tubo-ovarian abscess following a dilation and curettage (D&C) procedure in the setting of an ovarian dermoid cyst.

Regulation of interleukin-8 expression in human endometrial endothelial cells: a potential mechanism for the pathogenesis of endometriosis.

The elevation of the proinflammatory chemoattractant cytokine levels in ectopic and eutopic endometrium of endometriosis implies an inflammatory basis for this disease. The relationship between endothelial cells and leukocytes is likely to be important in the regulation of inflammatory mediators of endometriosis. The aim of this study was to describe the temporal and spatial expression of IL-8 in human endometrial endothelial cells (HEEC) in vivo and to compare the in vitro regulation of IL-8 expression by sex steroids in HEEC from women with or without endometriosis. Eutopic endometrial tissues and endometriosis implants were grouped according to menstrual cycle phase and examined by immunohistochemistry for IL-8 expression. Endothelial cells of endometriotic implants expressed higher IL-8 immunoreactivity compared with endothelial cells of eutopic endometrium from women with or without endometriosis (P < 0.02). For in vitro studies, HEEC were isolated from women with or without endometriosis and grown to preconfluence. The purity of cultured HEEC (90-95%) was confirmed by immunocytochemistry using endothelium-specific markers, CD31 and CD146. The effects of estradiol (5 x 10(-8) m), progesterone (10(-7) m), or both on IL-8 mRNA and protein levels were analyzed by RT-PCR and ELISA, respectively. Sex steroids reduced the expression of IL-8 mRNA and protein in HEEC from women without endometriosis. In contrast, both estradiol and progesterone stimulated IL-8 mRNA and protein expression in HEEC from women with endometriosis. We postulate that the stimulation of chemokine expression by sex steroids in HEEC of women with endometriosis may play a role in the inflammatory aspect of this disease.

Regulation of angiogenic activity of human endometrial endothelial cells in culture by ovarian steroids.

Blood vessel growth and regression in human endometrium are regulated throughout the menstrual cycle. We sought a direct role of ovarian steroids on human endometrial endothelial cell (HEEC) proliferation and vascularization. To investigate the HEEC angiogenicity of sex steroids, we developed a reliable method for the isolation of HEEC, which allowed us to investigate the angiogenic effects of sex steroids using immunohistochemistry, immunocytochemistry, Western blot, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt proliferation, and vascular tube formation analyses. We were able to obtain 95-99% pure HEEC with our isolation technique. HEEC expressed predominantly estrogen receptor beta, minimally expressed estrogen receptor alpha, and but did not express progesterone (P(4)) receptors A and B in vivo and in vitro. Estradiol (E(2); 10(-10)-10(-8) m) and P(4) (10(-12)-10(-8) m), alone or in combination, induced HEEC proliferation compared with control values after 48 h of treatment (P < 0.05). Furthermore, after 8 d of treatment, there were significantly more angiogenic patterns in E(2) (10(-8) m), P(4) (10(-10) m), and E(2) plus P(4) (10(-8) and 10(-10) m) treatment groups compared with the control group (angiogenic scores, 2.95 +/- 0.16, 3.26 +/- 0.16, 3.06 +/- 0.17, and 1.93 +/- 0.15, respectively; P < 0.01). In conclusion, our results suggest that there are direct effects of E(2) and P(4) on HEEC and provide a new understanding of the physiological role of sex steroids in the regulation of endometrial events such as angiogenesis.