Long pentraxin 3 and vitamin D receptor mRNA expression pattern of cumulus granulosa cells isolated from PCOS oocytes at different stages of nuclear maturation.

BACKGROUND: A fine-tuned pro-inflammatory and anti-inflammatory balance in the follicular unit is essential for cumulus expansion and successful ovulation. While the long pentraxin 3 (PTX3) gene is required for the expansion of cumulus cells (CCs), ovulation, resumption of meiosis and fertilization, the vitamin D receptor gene (VDR-X2) is required for intra-follicle redox balance. This study was planned to determine the expression pattern of VDR-X2 and PTX3 mRNA in CCs isolated from germinal vesicle (GV), metaphase I (MI), and metaphase II (MII) oocytes of PCOS patients with ovulatory dysfunction. METHODS: The relative expression of CC-PTX3 and CC-VDR-X2 mRNA were evaluated using qRT-PCR in a total of 79 CC samples collected from individual cumulus-oocyte complex of 40 infertile patients (20 PCOS and 20 non-PCOS normal responders) who underwent ovarian stimulation with the GnRH antagonist protocol. RESULTS: Relative PTX3 mRNA expressions of CCMI-control and CCMII-control showed 3- and 9-fold significant upregulation compared to CCGV-control, respectively. The relative PTX3 mRNA expression of CCMII-control increased approximately three fold compared to CCMI-control. Compared to CCGV-pcos, a 3-fold increase was noted in the relative PTX3 mRNA expression of CCMI-pcos and an approximately 4-fold increase in the PTX3 mRNA expression of CCMII-pcos. Relative PTX3 mRNA expression values of CCMII-pcos and CCMI-pcos were similar. A 6-fold upregulation of relative PTX3 mRNA and a 4-fold upregulation of VDR-X2 mRNA were detected in CCMII-control compared to CCMII-pcos. CC-VDR-X2 expression patterns of the PCOS and control groups overlapped with the CC-PTX3 pattern. Fertilization rates of the PCOS group exhibiting failed transcript expression were similar to normal responders. CONCLUSION: The fact that relative CC-PTX3 and CC-VDR mRNA expression does not increase during the transition from MI to MII stage in PCOS as in normal responders suggests that PTX3 and VDR expression may be defective in cumulus cells of PCOS patients with ovulatory dysfunction.

Endometrial Injury Upregulates Expression of Receptivity Genes in Women with Implantation Failure.

BACKGROUND: Homeobox genes A10 (HOXA10) and A11 (HOXA11), members of the abdominal B gene family, are responsible for embryonic survival and implantation. This study was planned to investigate whether endometrial injury alters the expression of both transcripts in women with implantation failure. METHODS: A total of 54 women with implantation failure were divided into two equal groups as experimental (scratching) and sham (no scratching). Participants in the scratching group were exposed to endometrial injury in the mid-luteal phase, and those in the sham group were exposed to endometrial flushing. The scratching group, but not the sham group, underwent prior endometrial sampling. A second endometrial sampling was performed on the scratching group in the mid-luteal phase of the following cycle. The mRNA and protein levels of the HOXA10 and 11 transcripts were determined in endometrial samples collected before and after injury/flushing. Participants in each group underwent IVF/ET in the cycle after the second endometrial sampling. RESULTS: Endometrial injury caused a 60.1-fold (p < 0.01) increase in HOXA10 mRNA and a 9.0-fold increase in HOXA11 mRNA (p < 0.02). Injury resulted in a significant increase in both HOXA10 (p < 0.001) and HOXA11 protein expression (p < 0.003). There was no significant change in HOXA10 and 11 mRNA expressions after flushing. Clinical pregnancy, live birth, and miscarriage rates of the both groups were similar. CONCLUSIONS: Endometrial injury increases homeobox transcript expression at both mRNA and protein levels.

Biomechanical Forces Determine Fibroid Stem Cell Transformation and the Receptivity Status of the Endometrium: A Critical Appraisal.

Myometrium cells are an important reproductive niche in which cyclic mechanical forces of a pico-newton range are produced continuously at millisecond and second intervals. Overproduction and/or underproduction of micro-forces, due to point or epigenetic mutation, aberrant methylation, and abnormal response to hypoxia, may lead to the transformation of fibroid stem cells into fibroid-initiating stem cells. Fibroids are tumors with a high modulus of stiffness disturbing the critical homeostasis of the myometrium and they may cause unfavorable and strong mechanical forces. Micro-mechanical forces and soluble-chemical signals play a critical role in transcriptional and translational processes' maintenance, by regulating communication between the cell nucleus and its organelles. Signals coming from the external environment can stimulate cells in the format of both soluble biochemical signals and mechanical ones. The shape of the cell and the plasma membrane have a significant character in sensing electro-chemical signals, through specialized receptors and generating responses, accordingly. In order for mechanical signals to be perceived by the cell, they must be converted into biological stimuli, through a process called mechanotransduction. Transmission of fibroid-derived mechanical signals to the endometrium and their effects on receptivity modulators are mediated through a pathway known as solid-state signaling. It is not sufficiently clear which type of receptors and mechanical signals impair endometrial receptivity. However, it is known that biomechanical signals reaching the endometrium affect epithelial sodium channels, lysophosphatidic acid receptors or Rho GTPases, leading to conformational changes in endometrial proteins. Translational changes in receptivity modulators may disrupt the selectivity and receptivity functions of the endometrium, resulting in failed implantation or early pregnancy loss. By hypermethylation of the receptivity genes, micro-forces can also negatively affect decidualization and implantation. The purpose of this narrative review is to summarize the state of the art of the biomechanical forces which can determine fibroid stem cell transformation and, thus, affect the receptivity status of the endometrium with regard to fertilization and pregnancy.

Genome-wide expression analysis of endometrium before and after endometrioma surgery.

OBJECTIVE: This study was planned to investigate possible alteration in the number of differentially expressed genes (DEGs) in eutopic endometrium before and after laparoscopic removal of the ovarian endometrioma. STUDY DESIGN: Six infertile women with ovarian endometrioma who underwent laparoscopic endometrioma cystectomy and six fertile control subjects who underwent tubal sterilization were included the study. Endometrial samples were collected before and 3 months after surgery throughout the mid-luteal phase. Genome-wide expression profiling was performed with Illumina Human HT-12V4 microchip, a high density silica bead-based microarray which utilizing more than 47.000 probs. Illumina microsequence system was used to assess detection of p value for each probe in every sample. Probes revealing significant assessment (p < .05) were selected for comparative analysis. RESULTS: We have detected 1478 DEGs in the comparison between endometrium of women with endometrioma and fertile controls. 118 out of 1478 genes (7.9 %) were significantly increased or decreased more than 1.5-fold in their expression. When the preoperative values of the control and patient groups are compared the number of DEGs was 243 (7.5 %). In 9 out of 243 genes, the fold change was found to be 1.5 and more (3.7 %). Comparison of the number of DEGs after endometrioma surgery and tubal ligation revealed that expression patterns of 1036 genes (33.7 %) were changed in endometrioma group. In 105 out of 1036 genes, the fold change was found to be 1.5 and above (10 %). A comparison using 2706 probes revealed changes in the expression patterns of 106 different genes (3.9 %) after endometrioma resection. In 4 out of 106 genes, the fold change was found to be 1.5 and above (3.7 %). The comparison using 6035 probes revealed changes in the expression patterns of 93 genes (1.5 %) after tubal ligation. None of the 93 genes had a fold change of 1.5 or higher. The number of DEGs in endometrioma groups after surgery was approximately 3-fold higher than control group. CONCLUSIONS: Endometrium of women with endometrioma displayed abnormal expression of genes associated with implantation, immunological, endocrine and neuracrine functions. Positive alteration of the expression pattern of DEGs and signal transduction pathways following endometrioma surgery can improve the receptive capacity and implantation rates of eutopic endometrium.

Intra-ovarian stem cell transplantation in management of premature ovarian insufficiency: towards the induced Oogonial Stem Cell (iOSC).

The specialized resident-stem cells in gonads are tasked with restorating damaged ovarian cells following injury to maintain sequential reproductive events. When we talk about premature ovarian insufficiency (POI) we accept the existence of decreased stem cell and their regenerative abilities. The present study was to explain how restorating damaged ovarian cells following injury to maintain sequential reproductive events in evidence-based medicine indexed in PubMed and Web of Science. The exact mechanism is unclear stem cells transfer may improve compromised ovarian function and fertility outcome in women with POI. Soluble factors secreted by stem cell may rescue impaired mitochondrial function in oogonial stem cells, enhance metabolic capacity of resident stem cells, induce local neovascularization in the ovary, and activate gene shifting between transferred stem cells and germ cell precursors. This review may provide insight into how stem cells show some of their beneficial effects on compromised ovarian microenvironment and germ cell niche and paves the way for clinical trials for improving ovarian function of women with POI. We also had the opportunity to share our hypothesis about the design and development of induced oogonial stem cell (iOSC) and its use in POI.

Laparoscopic Ovarian Drilling Improves Endometrial Homeobox Gene Expression in PCOS.

The study was designed to investigate whether laparoscopic ovarian drilling (LOD) of ovaries alters the expression levels of HOXA-10 and HOXA-11 mRNA in the endometrium of infertile women with clomiphene-resistant PCOS. Expression of HOXA-10 and HOXA-11 mRNA in the endometrium obtained before and after LOD during the midsecretory phase was measured. Expression of each gene was evaluated using real-time reverse transcriptase polymerase chain reaction (RT-PCR). Expression levels of HOXA-10 and HOXA-11 mRNA were lower in endometrium of patients with PCOS before LOD compared with fertile controls. But the differences failed to show statistical significance. Compared with fertile subjects, LOD of PCOS ovaries up-regulated endometrial HOXA-10 and HOXA-11 mRNA expression. Fold changes of HOXA-10 and HOXA-11 mRNA after LOD were found to be 4.46 and 4.19, respectively. Fold change increase in HOXA-10 and HOXA-11 mRNA was found to be statistically significant (P < .01, P < .02). There is a receptivity defect in the endometrium of women with PCOS that affects fertility regardless of other causes of infertility. LOD increases endometrial HOXA-10 and HOXA-11 mRNA expressions and improves receptivity in patients with clomiphene-resistant PCOS.

Molecular role of peptides/proteins in subfertility of polycystic ovarian syndrome.

Obesity and hyperandrogenemia are known to have adverse effects on both developing follicle and endometrium receptivity in polycystic ovarian syndrome (PCOS). Insulin resistance also contributes to this dilemma as a cause or a consequence and leads to worsening of the clinical picture. The difficulty in obtaining pregnancy despite the presence of a large number of oocyte has concentrated our attention on oocyte quality and development. However, the occurence of subfertility has also caused us to investigate the presence of different etiologic agents in non-obese PCOS women with normal androgen and insulin levels. In this context peptides have become the most accused and investigated molecules in cases of impaired fertility due to PCOS. Most of the studies investigating the relationship between PCOS and peptide did not support each other. The difficulties in measuring peptide levels as well as the individual variations in peptide synthesis and release are possible causes of this incongruity. For all these reasons, the incorporation of studies investigating the relationship between PCOS, peptide and subfertility in an article has become critical to pioneering future work. Understanding the association between peptides and subfertility will help us to understand the effects of peptides on failed fertility in PCOS. Moreover, updating our knowledge about peptides may allow us designing new drugs to to treat subfertility in PCOS. This review provides a general summary of the mechanisms of action of neuroendocrine peptides in regulating reproductive events. Since it is not usual to discuss all peptides in this context, only the effects of key central and peripheral peptides on fertility in PCOS have been extensively addressed.

Vaginal ultrasound-guided ovarian needle puncture compared to laparoscopic ovarian drilling in women with polycystic ovary syndrome.

STUDY OBJECTIVE: To compare pregnancy outcomes in PCOS women undergoing transvaginal ovarian injury (TVOI) and laparoscopic ovarian drilling (LOD) DESIGN: 126 infertile patients with PCOS were included in this prospective cohort study CANADIAN TASK FORCE CLASSIFICATION OF LEVEL OF EVIDENCE: IIA. SETTING: University-affiliated fertility center. PATIENTS: Sixty-seven infertile patients with the history of failed in vitro maturation underwent follow-up as the TVOI group. Fifty-nine infertile women who underwent LOD acted as controls. All subjects had PCOS with menstrual irregularity and were anovulatory by repetitive serum progesterone levels. INTERVENTIONS: The LOD group underwent six cauterizations of a single ovary with 30W for 4-6 s. Failed IVM subjects with 20-30 needle punctures per ovary acted as the TVOI group. Subjects were followed for six months. MEASUREMENTS AND MAIN RESULTS: There was not a significant difference between the groups when the cases were evaluated in terms of spontaneous pregnancy or miscarriage rates. BMI levels decreased in both the TVOI and the LOD groups in a similar fashion. However, serum AMH and AFC decreased greater after LOD than they did with TVOI over the six-month duration of the study (p < 0.001 in both cases). CONCLUSIONS: Preliminary data suggest that TVOI likely represents a safer, less costly and equally effective manner of surgical ovulation induction in anovulatory PCOS women when compared to LOD.

Fertility preservation in Turkey: a global look for nationwide strategy development

As the reproductive technology advanced along with the improved outcome in cancer treatment demands implementing new fertility preservation, developing algorithms on fertility preservation requires tailoring for each society. Here, the authors attempt to modify the current medical literature on fertility preservation for the Turkish population. A PubMed search was conducted using the search term fertility preservation. Initially, 280 items of literature were accessed. In the second evaluation, 126 articles were examined and 154 items were discarded due to the low quality of the literature. In the final round, only 68 publications that were the most relevant were found eligible for inclusion in this review article. In order to develop a more systematic national guideline, forming a multidisciplinary approach to create a web-based network would be the first step. Both physicians and patients will have open access to the information. This database should be linked to an international consortium to stay integrated and open for updating. The aim of this review was to evaluate the relationship between the current situation in our country and the developments in the world in light of the literature, and to establish infrastructure for the development of future approaches in our country.

Patatin-like phospholipase domain containing 3-gene (adiponutrin), preptin, kisspeptin and amylin regulates oocyte developmental capacity in PCOS.

This study was planned to test whether follicular fluid (FF) levels of patatin-like phospholipase domain containing 3-gene (PNPLA3:adiponutrin), preptin, kisspeptin, and amylin change in polycystic ovarian syndrome (PCOS). A total of 40 infertile volunteers undergoing IVF/ICSI were included in the study. They were divided into two groups as PCOS (n=20) and control group without PCOS (n=20). The controls were recruited from subjects with a poor ovarian response. The PCOS and control participants were matched according to their body mass index (BMI). Each group of participants underwent ovarian stimulation with GnRH antagonist protocol. Blood and FF samples of one dominant follicle were obtained from each subject during the oocyte pick-up. FF and serum levels of PNPLA3, preptin, kisspeptin and amylin were measured through ELISA. Amylin and adiponutrin median values were not different according to study groups (p>0.05). FF-preptin median values in the control group were similar to the serum preptin values of control and PCOS groups (Z=0.970, p=1.000 and Z=2.631, p=0.051, respectively). Medians of the serum preptin in control and PCOS groups were the same (Z=1.649; p=0.595). FF-preptin median values of PCOS group were significantly lower than the preptin median values of the control group. Serum preptin levels were positively correlated with HOMA-IR, but not with pregnancy rates and the number of retrieved oocytes. Serum kisspeptin levels were negatively correlated with the number of retrieved oocytes and pregnancy rates. While amylin and adiponutrin have no role in the folliculogenesis, kisspeptin and preptin work together for regulating follicle developmental capacity in PCOS.

Hypothesis: Co-transfer of genuine embryos and implantation-promoting compounds via artificial containers improve endometrium receptivity.

As with other organs endometrial functions are altered with the advancing age. Age related decrease in reproductive functions leads to decline in the number of oocytes retrieved and the synthesis of endometrial receptivity molecules. Despite the significant improvement in assisted reproductive technologies we do not have so many options to enhance endometrial receptivity. Due to lack of drugs having endometrium receptivity enhancement properties, oocyte donation seems to be the only solution for women with implantation failure. The euploid oocytes come from young and healthy donors may overcome age associated endometrial receptivity defect. Nevertheless, many reasons restrict us from using oocyte donation in women with implantation failure. We, therefore, hypothesized that by mimicking a young blastocyst's effect on endometrium, the transfer of genuine embryos and implantation-promoting compounds together might be the new treatment option for infertile women with recurrent implantation failure. Artificial beads, MI or GV oocytes, and empty zona can be used as a container for intrauterine replacement of implantation-promoting compounds.

The Investigation of Polymorphisms in DNA Repair Genes (XRCC1, APE1 and XPD) in Women with Polycystic Ovary Syndrome

Background: PCOS was reported to arise from the interaction of genetic and environmental factors. Some studies reported that women with PCOS have DNA damage and chromosome breakage. Such studies bring to mind the genes that are involved in DNA repairing. At present, several DNA repair genes and, as products of these genes, certain polymorphisms that alter the activity of proteins are known in the literature. The aim of this dissertation is to study the genomic instability that have been reported in PCOS cases along with the relationship between XRCC1 Arg194Trp, XRCC1 Arg399Gln, APE1 Asp148Glu, and XPD Lys751Gln polymorphisms in order to contribute to the pathogenesis of PCOS. Methods: Polymorphisms in DNA repair genes have been associated with the increased risk of various diseases and could also be related to the etiology of PCOS. Therefore, we conducted a study including 114 women with PCOS and 91 controls. These polymorphisms were determined by quantitative real time PCR and melting curve analysis using LightCycler. Results: Comparing the control groups at the end of the study, the results have not shown any statistically significant difference as far as XRCC1 Arg194Trp, XRCC1 Arg399Gln, and XPD Lys751Gln polymorphisms are concerned. However, there were notable differences between the groups in terms of APE1 Asp148Glu polymorphism. Associated with this condition, it has been noted that both mutant allele (Glu) frequency (37.72 % in the study group; 19.23% in the control group, p=0.0001) and homozygous mutant genotype (Glu/Glu) frequency (%12.28 in the study group; %6.60 in the control group, p=0.015) have been higher in the study group.

Impact of Endometrioma Resection on Eutopic Endometrium Metabolite Contents: Noninvasive Evaluation of Endometrium Receptivity.

The aim of this study was to determine whether endometrioma resection alters most commonly defined endometrial metabolites, lactate (Lac), N-acetylaspartate (NAA), creatine 1 (Cr1), creatine 2 (Cr2), and choline (Cho) during the window of implantation. Twenty patients with uni- or bilateral endometrioma and 7 patients having nonendometriotic benign ovarian cyst were included. Midluteal phase magnetic resonance spectroscopy analysis of eutopic endometrium was performed before surgery. Second spectrum of endometrium was obtained 3 to 5 months after laparoscopic endometrioma resection. Pre- and postoperative endometrial peaks of Lac, NAA, Cr, and Cho were measured in units and denominated in parts per million (ppm). Compared to preoperative peak values, significantly decreased NAA, Lac, and Cr1 signals were noted in patients undergoing endometrioma surgery. Nearly 5-fold decline in the NAA signal occurred after endometrioma surgery (1.94 ± 3.24 vs 0.37 ± 0.55). Likewise, 2.5-fold decline in Lac signals was noted after endometrioma resection (2.81 ± 2.64 vs 1.06 ± 1.88). Both uni- and bilateral endometrioma affected endometrium signals the same. The peak intensity of Cho, Cr1, Cr2, NAA, and Lac did not alter significantly after nonendometriotic cyst surgery. Endometrioma surgery straightens endometrial NAA, Lac, and Cr1 peaks, suggesting improvement in endometrial receptivity.

Surgery for Benign Gynecological Disorders Improve Endometrium Receptivity.

Regardless of the anatomical locations, some benign gynecological disorders (BGDs) such as peritoneal endometriosis, ovarian endometrioma, adenomyosis, uterine leiomyomas, endometrial polyps, uterine septum, and hydrosalpinges may lead to implantation failure. Despite progress in medical therapies, surgery remains a mainstay of BGDs treatment. Although our knowledge of endometrial receptivity after BGDs surgery is limited, it has allowed for significant improvement in the treatment of female subfertility. Many researchers studied on pregnancy outcome following BGDs surgery, but they did not investigate the possible impact of surgery on endometrial receptivity. They, therefore, concluded that pregnancy rates improved after BGDs surgery based on clinical observations. Many of these clinicians believe that surgical resection of BGDs leads to removal of local mechanical effect over the endometrium. Moreover, they accept that BGDs surgery may inhibit the detrimental signaling and secretion of some molecules from the BGDSs into the endometrium that may lead to favorable effect on the endometrium. However, so far, data from randomized controlled trials or systematic review or meta-analyses to answer the question whether surgical treatment of BGDs can improve endometrial receptivity are lacking. The purpose of this systematic review was to evaluate the results of available publications dealing with the impact of reproductive surgery for BGDs on endometrial receptivity.

Expression of Endometrial Receptivity Genes Increase After Myomectomy of Intramural Leiomyomas not Distorting the Endometrial Cavity.

This study was designed to investigate whether endometrial receptivity genes are altered in infertile patients with intramural leiomyomas (IM) not distorting the endometrial cavity undergoing myomectomy. We measured endometrial HOXA-10, HOXA-11, LIF, ITGB3, and ITGAV messenger RNA (mRNA) expressions levels before and after myomectomy/metroplasty during mid-luteal phase in participants with IM, submucosal leiomyomas (SM), and septate uterus and fertile participants without fibroids. Initial endometrial sampling was obtained at the time of surgery, and second sampling was obtained 3 months after myomectomy/metroplasty. Expressions of each gene were evaluated using real-time reverse transcriptase polymerase chain reaction (RT-PCR). A trend toward decreased endometrial HOXA-10, HOXA-11, and ITGAV mRNA expression was detected in both SM and IM groups before myomectomy when compared to both fertile group and septate uterus. However, the differences failed to show statistical significance. After myomectomy of IM, we have detected 12.8-fold increase in endometrial HOXA-10 mRNA expression and 9.0-fold increase in endometrial HOXA-11 mRNA expression. This increase in endometrial HOXA-10 and 11 mRNA expression was significant. Accordingly, 2 patients having intramural fibroids greater than 5 cm were able to remain pregnant after myomectomy. Conversely, submucosal myomectomy did not cause any significant effect on endometrial receptivity markers. Likewise, all markers of endometrial receptivity remained unchanged after metroplasty. Myomectomy of IM have favorable effect on endometrial HOXA-10 and 11 mRNA expression.

Selective Regulation of Oocyte Meiotic Events Enhances Progress in Fertility Preservation Methods.

Following early embryonic germ cell migration, oocytes are surrounded by somatic cells and remain arrested at diplotene stage until luteinizing hormone (LH) surge. Strict regulation of both meiotic arrest and meiotic resumption during dormant stage are critical for future fertility. Inter-cellular signaling system between the somatic compartment and oocyte regulates these meiotic events and determines the follicle quality. As well as the collected number of eggs, their qualities are also important for in vitro fertilization (IVF) outcome. In spontaneous and IVF cycles, germinal vesicle (GV)-stage oocytes, premature GV breakdown, and persistence of first meiotic arrest limit the reproductive performance. Likewise, both women with premature ovarian aging and young cancer women are undergoing chemoradiotherapy under the risk of follicle loss because of unregulated meiotic events. Understanding of oocyte meiotic events is therefore critical for the prevention of functional ovarian reserve. High levels of cyclic guanosine monophophate (cGMP), cyclic adenosine monophophate (cAMP) and low phosphodiesterase (PDE) 3A enzyme activity inside the oocyte are responsible for maintaining of meiotic arrest before the LH surge. cGMP is produced in the somatic compartment, and natriuretic peptide precursor C (Nppc) and natriuretic peptide receptor 2 (Npr2) regulate its production. cGMP diffuses into the oocyte and reduces the PDE3A activity, which inhibits the conversion of cAMP to the 5'AMP, and cAMP levels are enhanced. In addition, oocyte itself has the ability to produce cAMP. Taken together, accumulation of cAMP inside the oocyte induces protein kinase activity, which leads to the inhibition of maturation-promoting factor and meiotic arrest also continues. By stimulating the expression of epidermal growth factor, LH inhibits the Nppc/Npr2 system, blocks cGMP synthesis, and initiates meiotic resumption. Oocytes lacking the functional of this pathway may lead to persistence of the GV oocyte, which reduces the number of good quality eggs. Selective regulation of somatic cell signals and oocyte meiotic events enhance progress in fertility preservation methods, which may give us the opportunity to prevent follicle loss in prematurely aging women and young women with cancer are undergoing chemoradiotherapy.

Laparoscopic endometrioma resection increases peri-implantation endometrial HOXA-10 and HOXA-11 mRNA expression.

OBJECTIVE: To determine whether laparoscopic endometrioma resection alters peri-implantation endometrial HOXA-10, HOXA-11, LIF, ITGB3 and ITGAV mRNA expression. DESIGN: Case-control study. SETTING: Medical school. PATIENT(S): Twenty infertile patients with uni- or bilateral endometrioma, five infertile patients having nonendometriotic benign ovarian cyst, and five fertile control subjects. INTERVENTION(S): Mid-luteal-phase endometrial sampling was performed at the time of surgery. Second endometrial biopsies were obtained 3 months after laparoscopic endometrioma resection during the mid-luteal phase of the cycle. MAIN OUTCOME MEASURE(S): Endometrial HOXA-10, HOXA-11, LIF, ITGAV, and ITGB3 mRNA expressions were evaluated with the use of reverse-transcription polymerase chain reaction. RESULT(S): Significantly decreased endometrial ITGAV mRNA expression was noted in biopsies obtained from endometrioma and nonendometriotic cyst groups before surgery. Trends toward decreased endometrial HOXA-10, HOXA-11, LIF, and ITGB3 mRNA expressions were noted in the endometrioma and nonendometriotic cyst groups before surgery compared with the fertile subjects. However, the differences failed to show statistical significance. Compared with preoperative values, significantly increased HOXA-10 (12.1-fold change) and HOXA-11 (17.2-fold change) mRNA expressions were noted in endometrial biopsies obtained from subjects who were undergoing endometrioma surgery. Fold change in endometrial ITGAV mRNA after endometrioma surgery was found to be 30.1 and indicated a positive regulation. However, this fold increase was statistically insignificant. Expressions of these endometrial receptivity markers did not change significantly after surgical removal of nonendometriotic benign ovarian cysts. CONCLUSION(S): Laparoscopic endometrioma resection increases peri-implantation endometrial HOXA-10 and HOXA-11 mRNA expression, suggesting an improvement in endometrial receptivity.

Peptides: Basic determinants of reproductive functions.

Mammalian reproduction is a costly process in terms of energy consumption. The critical information regarding metabolic status is signaled to the hypothalamus mainly through peripheral peptides from the adipose tissue and gastrointestinal tract. Changes in energy stores produce fluctuations in leptin, insulin, ghrelin and glucose signals that feedback mainly to the hypothalamus to regulate metabolism and fertility. In near future, possible effects of the nutritional status on GnRH regulation can be evaluated by measuring serum or tissue levels of leptin and ghrelin in patiens suffering from infertility. The fact that leptin and ghrelin are antagonistic in their effects on GnRH neurons, their respective agonistic and antagonistic roles make them ideal candidates to use instead of GnRH agonist and antagonist. Similarly, kisspeptin expressing neurons are likely to mediate the well-established link between energy balance and reproductive functions. Exogenous kisspeptin can be used for physiological ovarian hyperstimulation for in-vitro fertilization. Moreover, kisspeptin antagonist therapy can be used for the treatment of postmenapousal women, precocious puberty, PCOS, endometriosis and uterine fibroids. In this review, we will analyze the central mechanisms involved in the integration of metabolic information and their contribution to the control of the reproductive function. Particular attention will be paid to summarize the participation of leptin, kisspeptin, ghrelin, NPY, orexin, urocortin, VIP, insulin, galanin, galanin like peptide, oxytocin, agouti gene-related peptide, and POMC neurons in this process and their possible interactions to contribute to the metabolic control of reproduction.

Serum salusins levels are increased and correlated positively with cyst size in ovarian endometrioma.

OBJECTIVES: The objective of this study is to evaluate plasma concentrations of salusin-α and salusin-ß levels in women with endometrioma and non-endometriotic benign ovarian cysts. METHOD: Endometrioma patients (n = 14), non-endometriotic ovarian cysts (n = 14), and age-matched normal healthy fertile subjects (n = 14) participated in this study. Plasma salusin-α and salusin-ß levels at the time of mid-luteal phase before and 3 months after L/S cystectomy were measured using ELISA and EIA tests, and their relation with demographic parameters was also assessed. RESULTS: The mean salusin-α and salusin-ß levels were significantly higher in women with endometrioma before the removal of cyst compared with cases with non-endometriotic cyst and fertile cases. Surgical removal of the endometrioma decreased the mean salusin-α and salusin-ß levels to the level of those with non-endometriotic cyst before and after the cystectomy and fertile women, in both unilateral and bilateral endometrioma cases. Plasma salusin-ß concentrations were found to be positively correlated with age, size of cyst, bilaterality, and salusin-α levels. Salusin-ß values showed no correlations to BMI and size of the ovarian cysts. CONCLUSIONS: Plasma salusin-α and salusin-ß levels are increased in endometrioma patients and positively correlated with endometrioma size. Laparoscopic removal of the endometrioma by stripping technique decreases the salusin levels to a similar level of fertile women.