Cysteine-Cysteine Motif Chemokine Receptor 5 Expression in Letrozole-Induced Polycystic Ovary Syndrome Mice.

Polycystic ovary syndrome (PCOS), which affects 5-10% of women of reproductive age, is associated with reproductive and metabolic disorders, such as chronic anovulation, infertility, insulin resistance, and type 2 diabetes. However, the mechanism of PCOS is still unknown. Therefore, this study used a letrozole-exposed mouse model in which mice were orally fed letrozole for 20 weeks to investigate the effects of letrozole on the severity of reproductive and metabolic consequences and the expression of cysteine-cysteine motif chemokine receptor 5 (CCR5) in letrozole-induced PCOS mice. The letrozole-treated mice showed a disrupted estrous cycle and were arrested in the diestrus phase. Letrozole treatment also increased plasma testosterone levels, decreased estradiol levels, and caused multicystic follicle formation. Furthermore, histological analysis of the perigonadal white adipose tissue (pgWAT) showed no significant difference in the size and number of adipocytes between the letrozole-treated mice and the control group. Further, the letrozole-treated mice demonstrated glucose intolerance and insulin resistance during oral glucose and insulin tolerance testing. Additionally, the expression of CCR5 and cysteine-cysteine motif ligand 5 (CCL5) were significantly higher in the pgWAT of the letrozole-treated mice compared with the control group. CCR5 and CCL5 were also significantly correlated with the homeostasis model assessment of insulin resistance (HOMA-IR). Finally, the mechanisms of insulin resistance in PCOS may be caused by an increase in serine phosphorylation and a decrease in Akt phosphorylation.

A novel GnRH-antagonist protocol by switching to medroxyprogesterone when patients being at risk of ovarian hyperstimulation syndrome during ovarian stimulation.

BACKGROUND/PURPOSE: To investigate whether switching GnRH antagonist (GnRHant) to medroxyprogesterone acetate (MPA) sequentially in the middle of controlled ovarian stimulation could effectively prevent premature LH surge in a GnRHant protocol in patients turn out to be at a high risk of ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. METHODS: This is a retrospective cohort study. RESULTS: Premature LH surge did not occur in both groups of patients. The switch protocol group had a significantly fewer days of GnRHant treatment (3.1 ± 1.0 vs. 6.5 ± 1.2) compared with GnRHant protocol group. The mean duration of MPA treatment was 3.6 ± 1.1 days. There were no statistically significant differences in terms of live birth, implantation, and clinical pregnancy rates. CONCLUSION: This study showed that MPA could sequentially replace GnRHant and effectively prevent premature LH surge after several days of GnRHant administration in patients being at high risk of OHSS during controlled ovarian stimulation. Switch protocol could individualize freeze-all policy and reduce the injection burden of GnRHant.

Psychological health of women who have conceived using assisted reproductive technology in Taiwan: findings from a longitudinal study.

BACKGROUND: Despite the increasing use of Assisted Reproductive Technology (ART) and the significant physical and emotional commitments that these treatments and procedures involve, only limited evidence exists regarding the psychological health of women who undergo ART. This study investigated the changes over time in the psychological health of women who have conceived using ART during the first, second, and third trimesters of pregnancy and during the postpartum period in Taiwan. METHODS: A quantitative longitudinal study was conducted at a fertility centre in Taiwan. 158 pregnant women who had conceived using ART completed a web-based questionnaire that included the following instruments: State Anxiety Inventory, Edinburgh Postnatal Depression Scale, Modified Maternal Foetal Attachment Scale, Pregnancy Stress Rating Scale, Maternity Social Support Scale, Intimate Bond Measure, and Parenting Stress Index. The data were collected the first (9-12 weeks), second (19-22 weeks), third (28-31 weeks) trimesters of pregnancy and at 7-10 weeks postpartum. RESULTS: Levels of anxiety and depression, which are both key indicators of psychological health, were highest during the first trimester, with scores of 42.30 ± 11.11 and 8.43 ± 4.44, respectively. After the first trimester, anxiety scores decreased and remained stable through the remainder of pregnancy, with scores of 38.03 ± 10.58 in the second and 38.39 ± 10.36 in the third trimester, but increased at two-months postpartum, attaining a score of 41.18 ± 11.68. Further, depression scores showed a similar pattern, declining to a mean of 7.21 ± 4.23 in the second and 6.99 ± 4.11 in the third trimester and then increasing to 8.39 ± 5.25 at two-months postpartum. Pregnancy stress and social support were found to be the most important predictors of change in psychological health during pregnancy and the postpartum period. CONCLUSION: Psychological health was found to be poorest during the first trimester and at two-months postpartum. Moreover, pregnancy stress and social support were identified as key predictors of change in psychological health. The findings indicate a need for increased sensitivity among healthcare professionals to the psychological vulnerability of women who have conceived using ART as well as a need to introduce tailored interventions to provide appropriate psychological support to these women.

Feasibility of corifollitropin alfa/GnRH antagonist protocol combined with GnRH agonist triggering and freeze-all strategy in polycystic ovary syndrome patients.

BACKGROUND/PURPOSE: The long-acting corifollitropin alfa is comparable to FSH in terms of pregnancy outcomes in normal responders and poor responders. Corifollitropin alfa has never been studied in polycystic ovary syndrome (PCOS) patients because of concerns of excessive ovarian stimulation and ovarian hyperstimulation syndrome (OHSS). The purpose of the study was to evaluate if corifollitropin alfa can be used in PCOS patients. METHODS: Forty PCOS patients who were going to undergo in vitro fertilization were enrolled in this study. A single injection of corifollitropin alfa was administered on cycle day 2 or day 3. From stimulation day 8 onwards, daily FSH was administered until the day of final oocyte maturation. Cetrorelix was administered from stimulation day 5 to prevent premature LH surge. Final oocyte maturation was triggered by: acetate. All embryos were cryopreserved and replaced in subsequent cycles. RESULTS: All 40 patients were subjected to oocyte retrieval, and none developed moderate or severe ovarian hyperstimulation syndrome (0%, 95% CI 0-0.088). For each patient, an average of 23.4 (±7.4; 95% CI 21.0-25.7) oocytes were retrieved and a mean of 11.7 (±6.4; 95% CI 9.6-13.8) embryos were frozen. Mean serum estradiol level on the day of GnRHa triggering was 7829.9 pg/ml (±3297; 95% CI 6775-8885). The cumulated ongoing pregnancy rate after 3 frozen-thawed embryo transfers was 75.0% (95% CI 61.6%-88.4%). CONCLUSION: The results suggest that corifollitropin alfa/GnRH antagonist protocol can be used in PCOS patients, in combination with GnRHa triggering and embryo cryopreservation.

Reduced uterine receptivity for mouse embryos developed from in-vitro matured oocytes.

PURPOSE: The outcomes of in-vitro maturation (IVM) are inferior compared to those of IVF. The purpose of the study was to compare the implantation rates of IVM- and in-vivo maturation (IVO)- derived embryos, and to evaluate their effects on uterine receptivity. METHODS: The IVM- and IVO- oocytes were obtained from female mice, fertilized and transferred to separate oviducts of the same pseudo-pregnant mice. After 5 days, the implanted blastocysts were dissected out of the uterine horns, and the uterine horns were analyzed for the expression of mRNAs encoding leukemia inhibitory factor, heparin-binding epidermal growth factor, insulin-like growth factor binding protein-4, progesterone receptor, and Hoxa-10. RESULTS: The maturation rate of the IVM- oocytes was 81.2%. The fertilization rate of the IVM oocytes was lower than that of the IVO oocytes (50.5% vs. 78.0%, p = 0.038), as was their implantation rate (14.5% vs. 74.7%, p < 0.001). All 5 mRNAs examined were expressed at significantly lower levels in the uterine horns that received the IVM-derived embryos than in those that received the IVO-derived embryos. CONCLUSIONS: The IVM-derived embryos are less competent in inducing expression of implantation-related mRNAs in the uterine horn.

Efficacy of hysteroscopic cervical resection for cervical stenosis.

STUDY OBJECTIVE: Cervical stenosis can be an impediment to embryo transfer (ET) and intrauterine insemination (IUI). We propose a technique of hysteroscopic cervical resection to overcome cervical stenosis. DESIGN: Prospective clinical study (Canadian Task Force classification III). SETTING: Private general hospital. PATIENTS: Forty-three infertile women in whom trial ET or IUI had failed with 3 available catheters. INTERVENTIONS: The procedure was performed with a hysteroscope under ultrasound guidance. Starting from the external os, the loop electrode gradually resected protrusions and cervical tissue until the hysteroscope could enter the uterine cavity. Repeat trial ET/IUI was performed 1 month later. The women who became pregnant underwent sonographic measurement of the cervical length and dilatation in the second and third trimesters. MEASUREMENTS AND MAIN RESULTS: Excluding 13 patients in whom the sound could pass through the cervical canal after anesthesia, 30 patients were included for analysis. The procedure failed in 1 patient (3.3%). The mean operation time was 18.0 (±7.4) minutes. Repeat trial ET/IUI was successful in all patients. There were 5 twin pregnancies and 9 singleton pregnancies after IUI or ET. From the 5 women with twin pregnancies; 2 underwent premature delivery at 34 weeks; and 3 underwent elective cesarean delivery at 35, 36, and 37 weeks, respectively. From the 9 women with singleton pregnancies, 1 underwent cesarean section at 36 weeks because of preeclampsia, and the other 8 delivered at term. CONCLUSION: Hysteroscopic cervical resection is a safe and effective treatment for cervical stenosis.

Aquaglyceroporin-7 overexpression in women with the polycystic ovary syndrome.

BACKGROUND: Aquaglyceroporin-7 (AQP7) is an adipose glycerol channel protein that has been suggested to be involved in whole-body glucose homeostasis and insulin sensitivity. The aim of this study was to investigate the expression of AQP7 in visceral adipose tissues from women with the polycystic ovary syndrome (PCOS). METHODS: AQP7 mRNA and protein levels were measured in omental adipose tissue from 5 women with the PCOS and 4 healthy controls matched for body mass index and age; this was done by the real-time polymerase chain reaction (PCR) and Western blotting. - RESULTS: The women with the PCOS had significantly higher homeostasis model insulin resistance indices (HOMA) and their quantitative insulin sensitivity check indices were significantly lower compared to the controls (p < 0.05). No significant difference was noted between the two groups for the plasma glycerol concentration. AQP7 mRNA expression and protein levels in omental adipose tissue from women with the PCOS were significantly higher than those of the controls (p = 0.007). AQP7 expression showed a positive correlation with fasting insulin levels, insulin levels at 2 h after glucose loading and HOMA in women with the PCOS. CONCLUSION: AQP7 overexpression may be related to insulin sensitivity and glucose homeostasis in women with the PCOS.

Combination of cabergoline and embryo cryopreservation after GnRH agonist triggering prevents OHSS in patients with extremely high estradiol levels--a retrospective study.

PURPOSE: Embryo cryopreservation after triggering oocyte maturation with GnRH agonist (GnRHa) in GnRH antagonist protocols has been proposed to prevent ovarian hyperstimulation syndrome (OHSS). However, a small percentage of patients still developed severe OHSS. The purpose of the study was to investigate the efficacy of preventing OHSS in patients at very high risk when cabergoline was given in addition to elective cryopreservation after GnRHa triggering. METHODS: This is a retrospective observational study. The patients were stimulated with GnRH antagonist protocol. When serum E2 concentration was >6,000 pg/ml and there were more than 20 follicles ≥11 mm on the day of final oocyte maturation, GnRHa was used to trigger oocyte maturation. Cabergoline was given to augment the effect of preventing OHSS. The embryos were electively cryopreserved by vitrification and thawed in subsequent cycles. The primary outcome measure was the incidence of severe OHSS. The secondary outcome measure was the clinical pregnancy rate in the first frozen-thawed embryo transfer cycle. RESULTS: One hundred and ten patients underwent 110 stimulated cycles were included for analysis. No patients developed moderate/severe OHSS. Mean E2 concentration on the day of final oocyte maturation was 7,873 pg/ml, and an average of 22.7 oocytes was obtained from each patient. One hundred and ten thawing cycles were performed, resulting in 69 clinical pregnancies (62.7 %). CONCLUSIONS: Combining cabergoline and embryo cryopreservation after GnRHa triggering in GnRH antagonist protocol could prevent OHSS in patients at very high risk.

Transvaginal sono-guided aspiration of gestational sac concurrent with a local methotrexate injection for the treatment of unruptured cesarean scar pregnancy.

PURPOSE: Cesarean scar pregnancy (CSP) is one of the rarest forms of ectopic pregnancy. A delay in treatment can lead to massive bleeding, uterine rupture, and life-threatening maternal morbidity. We present a conservative method for the management of CSP at a single tertiary centre over a 6-year period. METHODS: Eleven patients with unruptured CSPs who were treated by transvaginal aspiration of the gestational sac followed by a local methotrexate injection were evaluated. RESULTS: Gestational age at diagnosis ranged from 5 + 2 weeks to 7 + 4 weeks. Seven of the patients had undergone two prior Caesarean sections (63.6 %). The levels of ß-hCG at the time of diagnosis ranged from 1,290 to 81,586 mIu/ml. The mean time of the procedure was 8.2 ± 1.6 min. During follow up, 54.5 % of the patients may need an additional systemic MTX injection due to an elevation of ß-hCG. Estimated blood loss of the procedure was <50 ml and no blood transfusion is needed. This method has a shorter operative time, less blood loss and no hospitalization is needed for CSPs. All patients had their uterus successfully preserved without maternal morbidity or mortality. CONCLUSIONS: Transvaginal sono-guided sac aspiration concurrent with a local MTX injection is an effective management option for preserving the fertility of women with an unruptured CSP. However, additional systemic MTX injection may be needed if ß-hCG levels >20,000 mIU/ml at diagnosis.

Cytogenic and molecular analyses of 46,XX male syndrome with clinical comparison to other groups with testicular azoospermia of genetic origin.

BACKGROUND/PURPOSE: XX male is a rare sex chromosomal disorder in infertile men. The purpose of this study was to distinguish the clinical and genetic features of the 46,XX male syndrome from other more frequent, testicular-origin azoospermic causes of male infertility. METHODS: To study 46,XX male syndrome, we compared clinical and endocrinological parameters to other groups with testicular-origin azoospermia, and to an age-matched group of healthy males and females as normal control. Fluorescent in situ hybridization for detection and localization of the sex-determining region of the Y gene (SRY), array-based comparative genomic hybridization screening, and real-time qualitative polymerase chain reaction of FGF9, WT1, NR5A1, and SPRY2 genes were performed in this genetic investigation. RESULTS: Our three patients with 46,XX male syndrome had a much higher follicular-stimulating hormone level, lower body height, lower testosterone level, and ambiguous external genitalia. One of the three patients with 46,XX male syndrome was SRY-negative. A further genetic study, including a comparative genomic hybridization array and real-time polymerase chain reaction, showed a gain of FGF9 copy numbers only in the SRY-negative 46,XX male. The genetic copy number of the FGF9 gene was duplicated in that case compared to the normal female control and was significantly lower than that of the normal male control. No such genomic gain was observed in the case of the two SRY-positive 46,XX males. CONCLUSION: Similar to clinical manifestations of 46,XX male syndrome, genetic evidence in this study suggests that FGF9 may contribute to sex reversal, but additional confirmation with more cases is still needed.

Factors associated with postpartum depressive symptoms among women who conceived with infertility treatment.

Infertility treatment experiences may accumulate and influence postpartum psychological well-being among women with infertility. However, the association between infertility treatment experiences and postpartum depressive symptoms remained unclear. This cross-sectional survey aimed to describe depressive symptom scores of 180 women, who conceived while undergoing infertility treatment, at 2-6 months after childbirth, and to explore factors, including infertility history and treatment experiences, associated with postpartum depressive symptoms. Data were collected via telephone interviews and patient record reviews. Postpartum depressive symptoms were measured using the Edinburgh Postnatal Depression Scale, with a cutoff score of 10. The prevalence of postpartum depressive symptoms was 34.4 %. Higher perceived stress levels after childbirth than before undergoing infertility treatment, a duration of infertility diagnosis longer than three years, maternal age >35 years, pregnancy conceived through in vitro fertilization (IVF), and experiencing all three lines of infertility treatment, namely ovarian stimulation, intrauterine insemination, and IVF, were associated with a higher risk of postpartum depressive symptoms. Breastfeeding, social support, and baby sex in line with stated preference were negatively associated with postpartum depressive symptoms. There were no significant interactions between the variables. The women's infertility history and treatment experiences were found to have influenced their postpartum depressive symptoms, especially among women who had a long duration of infertility, conceived through IVF, and had received all lines of infertility treatment.

Expression levels of vascular cell adhesion molecule-1 in young and nonobese women with polycystic ovary syndrome.

BACKGROUND/AIMS: The objective of this study was to measure levels of mRNAs for inflammatory markers and resistin in human peripheral blood mononuclear cells (PBMCs) in young and nonobese women with polycystic ovary syndrome (PCOS). METHODS: Fifteen young, nonobese women with PCOS and 10 age-matched controls were enrolled in this study. Levels of mRNAs for resistin and the inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human PBMCs were measured using real-time PCR. RESULTS: The mean age and BMI of the women with PCOS were 27.54 ± 6.3 years and 27.4 ± 5.7, respectively. The women with PCOS had significantly higher fasting and 2-hour insulin levels, homeostasis model assessment of insulin resistance index (HOMA(IR)) and total cholesterol levels than the controls. VCAM-1 and ICAM-1 mRNA levels were significantly higher in women with PCOS than in controls, whereas no differences in resistin, IL-6, TNF-α and MCP-1 mRNA levels were observed between the groups. After adjusting for the BMI, only VCAM-1 mRNA levels were significantly higher in women with PCOS than in controls and correlated with the HOMA(IR) and total cholesterol. CONCLUSION: Elevated VCAM-1 in human PBMCs in young, nonobese women with PCOS is associated with insulin resistance, independent of the BMI.

Expression of visfatin mRNA in peripheral blood mononuclear cells is not correlated with visfatin mRNA in omental adipose tissue in women with polycystic ovary syndrome.

BACKGROUND: Visfatin, which is secreted predominantly from visceral adipose tissue, has an insulin-mimetic action and may play a role in the regulation of insulin sensitivity in humans. Peripheral blood mononuclear cells (PBMCs) from venous blood samples are the most accessible tissue for the analysis of gene expression. The aims of the study were to compare the expression of visfatin in PBMCs with that in omental adipose tissue in women with polycystic ovary syndrome (PCOS). METHODS: Visfatin mRNA was measured in omental adipose tissue and PBMCs from 10 women with PCOS and 10 healthy controls, matched for BMI and age, using the real-time polymerase chain reaction (PCR). RESULTS: The expression of visfatin mRNA in both omental adipose tissue and PBMCs from the women with PCOS was significantly higher (P = 0.01 and P = 0.05, respectively) than that in the controls. This finding indicated that mononuclear cells are a potential source of visfatin in women with PCOS. However, only the expression of visfatin mRNA in adipose tissue, not that in PBMCs, showed a significant positive correlation with insulin levels 2h after glucose loading (P = 0.044, r(2) = 0.45), and with homeostasis model assessment-insulin resistance (HOMA(IR); P = 0.035, r(2) = 0.47). In addition, the expression of visfatin mRNA in PBMCs did not correlate with the expression of visfatin mRNA in omental adipose tissue. CONCLUSIONS: PCOS is associated with increased visfatin mRNA concentrations in PBMCs and in omental adipose tissue. However, only visfatin mRNA concentration in omental adipose tissue is closely correlated with BMI and insulin resistance.

Expression levels of haem oxygenase-1 in the omental adipose tissue and peripheral blood mononuclear cells of women with polycystic ovary syndrome.

BACKGROUND: Haem oxygenase (HO)-1, an enzyme that degrades haem, plays a key role in the regulation of the inflammatory response and insulin resistance. The aim of this study was to evaluate the role of HO-1 in the regulation of insulin resistance and glucose tolerance in women with polycystic ovary syndrome (PCOS). METHODS: Omental adipose tissue and human peripheral blood mononuclear cells (PBMCs) from seven women with PCOS and five healthy controls, matched for BMI and age, were analysed using western blotting and the real-time PCR. RESULTS: Women with PCOS were found to have significantly higher fasting and 2-h insulin levels, a significantly higher homeostasis model assessment insulin resistance index and a lower fasting glucose-to-insulin ratio (G(0)/I(0)) than the controls. The level of HO-1 protein in omental fat (P = 0.002), and the expression of HO-1 mRNA in omental fat and PBMCs from the women with PCOS were significantly lower (P = 0.002 and 0.05, respectively) than those of the controls. The expression of adiponectin mRNA in omental fat was also significantly lower (P = 0.02) in the women with PCOS than in the controls. However, there were no significant differences in the expression of tumour necrosis factor-α or interleukin-6 between the two groups. The level of HO-1 protein showed a significant positive correlation with the expression of HO-1 mRNA (r(2) = 0.786, P = 0.037) and adiponectin mRNA (r(2) = 0.7276, P <0.05). Serum insulin and glucose levels and BMI showed a significant negative correlation with the level of HO-1 (P< 0.05). CONCLUSIONS: Our results suggest that the HO-1-adiponectin axis may be associated with the regulation of insulin resistance and glucose intolerance in women with PCOS.

Effect of incubation with different concentrations and durations of FSH for in-vitro maturation of murine oocytes.

The purpose of the study was to evaluate whether a lower concentration of FSH or 2-h incubation with FSH would improve the outcome of in-vitro maturation of oocytes. The immature oocytes were obtained from FVB mice, and were allocated to four groups and incubated in the maturation media for 24 h. The maturation media were supplemented with 10 mIU/ml FSH for 24 h (group 1), 10 mIU/ml FSH for 2 h (group 2), 75 mIU/ml FSH for 24 h (group 3) or 75 mIU/ml FSH for 2 h (group 4). In each group, half of the in-vitro-matured oocytes were fertilized and cultured to blastocysts and the remaining matured oocytes were analysed for growth differentiation factor (GDF)-9 and bone morphogenetic protein (BMP)-15 mRNA to assess the oocyte quality. The maturation rates and oocyte BMP-15 mRNA concentrations were similar among the four groups. The GDF-9 mRNA concentrations were similar in group 2 and group 4. The fertilization and blastocyst rates were higher in groups 2 and 4 than in groups 1 and 3. It is concluded that 2-h incubation with FSH is better than 24-h incubation in terms of the fertilization rate and blastocyst development.

P16 methylation is an early event in cervical carcinogenesis.

BACKGROUND: Aberrant gene promoter methylation is a critical event in tumorigenesis. The aim of this study was to explore the promoter hypermethylation of p16 and DAPK1 during the progression of cervical precancerous lesions. METHODS: A series of 98 cervical neoplasms (72 cervical intraepithelial neoplasia and 26 cervical carcinomas) were evaluated. The promoter methylation status of p16 and DAPK1 was assessed from cervical scrapings by methylation-specific polymerase chain reaction. RESULTS: For p16, the frequency of promoter hypermethylation showed an increasing trend from normal to dysplastic to invasive squamous cancer specimens, and this increase reached statistical significance (P < 0.0001). However, there was no significant difference in the promoter methylation state of DAPK1 with regard to the various grades of cervical lesions (P = 0.077). Specifically, methylation of p16 was a frequent event in the cervical carcinoma samples, and these figures were statistically significant compared with the normal and cervical intraepithelial neoplasia I cases (P = 0.015 and P = 0.021, respectively). CONCLUSIONS: These results imply that promoter hypermethylation of p16 occurs at an early stage of cervical neoplastic progression. This early event may play an initiating role in the malignant transformation of low-grade dysplasia into high-grade dysplasia and invasive carcinoma. We suggest that aberrant promoter methylation of p16 may serve as a useful biomarker during the follow-up of low-grade dysplasia.

Progestin primed ovarian stimulation using corifollitropin alfa in PCOS women effectively prevents LH surge and reduces injection burden compared to GnRH antagonist protocol.

Utilizing corifollitropin alfa in GnRH antagonist (GnRHant) protocol in conjunction with GnRH agonist trigger/freeze-all strategy (corifollitropin alfa/GnRHant protocol) was reported to have satisfactory outcomes in women with polycystic ovary syndrome (PCOS). Although lessening in gonadotropin injections, GnRHant were still needed. In addition to using corifollitropin alfa, GnRHant was replaced with an oral progestin as in progestin primed ovarian stimulation (PPOS) to further reduce the injection burden in this study. We try to investigate whether this regimen (corifollitropin alfa/PPOS protocol) could effectively reduce GnRHant injections and prevent premature LH surge in PCOS patients undergoing IVF/ICSI cycles. This is a retrospective cohort study recruiting 333 women with PCOS, with body weight between 50 and 70 kg, undergoing first IVF/ICSI cycle between August 2015 and July 2018. We used corifollitropin alfa/GnRHant protocol prior to Jan 2017 (n = 160), then changed to corifollitropin alfa/PPOS protocol (n = 173). All patients received corifollitropin alfa 100 µg on menstruation day 2/3 (S1). Additional rFSH was administered daily from S8. In corifollitropin alfa/GnRHant group, cetrorelix 0.25 mg/day was administered from S5 till the trigger day. In corifollitropin alfa/PPOS group, dydrogesterone 20 mg/day was given from S1 till the trigger day. GnRH agonist was used to trigger maturation of oocyte. All good quality day 5/6 embryos were frozen, and frozen-thawed embryo transfer (FET) was performed on subsequent cycle. A comparison of clinical outcomes was made between the two protocols. The primary endpoint was the incidence of premature LH surge and none of the patients occurred. Dydrogesterone successfully replace GnRHant to block LH surge while an average of 6.8 days of GnRHant injections were needed in the corifollitropin alfa/GnRHant group. No patients suffered from ovarian hyperstimulation syndrome (OHSS). The other clinical outcomes including additional duration/dose of daily gonadotropin administration, number of oocytes retrieved, and fertilization rate were similar between the two groups. The implantation rate, clinical pregnancy rate, and live birth rate in the first FET cycle were also similar between the two groups. In women with PCOS undergoing IVF/ICSI treatment, corifollitropin alfa/PPOS protocol could minimize the injections burden with comparable outcomes to corifollitropin alfa/GnRHant protocol.

Increased regulated on activation, normal T-cell expressed and secreted levels and cysteine-cysteine chemokine receptor 5 upregulation in omental adipose tissue and peripheral blood mononuclear cells are associated with testosterone level and insulin resistance in polycystic ovary syndrome.

OBJECTIVE: To study the relationship between circulating chemokine cysteine-cysteine motif ligand (CCL) 5 levels and cysteine-cysteine chemokine receptor type 5 (CCR5) expression in peripheral blood mononuclear cells (PBMCs) and adipose tissue with hyperandrogenism and insulin resistance in patients with polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: University teaching hospital. PATIENT(S): Fifteen women with PCOS and 15 controls matched for body mass index and age were enrolled in this study. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Plasma levels of CCL3, CCL4, and CCL5 were determined using enzyme-linked immunosorbent assay kits, and omental adipose tissue and PBMCs were analyzed using real-time polymerase chain reaction to determine the expression level of CCR5 in participants. RESULT(S): Levels of CCL5 were significantly higher in women with PCOS. Expression of CCR5 in adipose tissue and PBMCs was significantly higher in women with PCOS compared with that in women in the control group. Cysteine-cysteine chemokine receptor type 5 expression also was upregulated in THP-1 cells after chronic exposure to testosterone. Levels of CCL5 had a significant positive correlation with testosterone levels in women with PCOS. Moreover, CCR5 showed a positive correlation with fasting glucose levels, homeostasis model insulin resistance index, and C-reactive protein. CONCLUSION(S): Increased levels of CCL5 and overexpression of CCR5 in PBMCs and adipose tissue are associated with hyperandrogenism and insulin resistance in women with PCOS. Additionally, CCR5 and CCL5 may be used as biomarkers in the pathogenesis of PCOS.

Omental fat receptor interacting protein 140 mRNA expression in women with polycystic ovary syndrome.

BACKGROUND: Receptor interacting protein 140 (RIP140) is a co-repressor and essential for oocytes released by the ovary during ovulation. The aim of the study is to investigate adipose mRNA expression of RIP140 in women with polycystic ovary syndrome (PCOS) before and 3 months after laparoscopic ovarian electrocauterization (LOE). METHODS: Adipose tissues obtained from 15 women with PCOS before and after LOE were analyzed. Ten lean, age- and BMI-matched non-PCOS women served as controls. Gene expression of RIP140 was quantified by reverse transcriptase-polymerase chain reaction. RESULTS: The overall spontaneous ovulation rate was 73.3% in PCOS after the LOE procedure. However, no difference was found in the expression of RIP140 between women with PCOS before LOE and controls or between PCOS before and after LOE. No difference was found in RIP140 expression between obese and lean women with PCOS, or between obese PCOS and lean controls. Further, there was no correlation between RIP140 and fasting or 2-hour glucose or insulin, homeostasis model insulin resistance index (HOMA(IR)), and fasting glucose-to-insulin ratio (G(0)/I(0)) in women with PCOS. CONCLUSION: RIP140 gene does not play any pivotal role in the process of ovulation, insulin resistance or fat accumulation in women with PCOS.