Endocrinology AND Infertility, female [keywords]
- Hysteroscopic polypectomy without cycle cancellation in IVF/ICSI cycles: a cross-sectional study. [JOURNAL ARTICLE]
- Eur J Obstet Gynecol Reprod Biol 2016 Aug 10.:37-42.
To evaluate the effect of hysteroscopic polypectomy during ovarian stimulation phase on in vitro fertilization and/or intracytoplasmic sperm injection (IVF/ICSI) cycles outcomes.This cross sectional study was performed in female infertility department of Royan Institute from January 2011 to December 2013. In total, 160 patients who were diagnosed incidentally polyp/polyps less than 20mm during the stimulation phase for oocyte recoveries were recruited; of these, fifty eight cases underwent hysteroscopic polypectomy without cycle cancellation non-randomly. Polyp resection was performed through hysteroscopic polypectomy during ovarian stimulation. The interval between polypectomy and embryo transfer (ET) was 3-17 days. The women who did not undergo hysteroscopic polypectomy and matched for polyp size were selected as control group. The outcomes of IVF/ICSI cycles were compared between groups.The data analysis showed the two groups were comparable in terms of patients' characteristics and stimulation outcomes. The implantation rate was not significantly different between groups (P=0.3). The clinical pregnancy and live birth rates were similar between groups (%34.9 vs. %32.5 and %30.2 vs. %27.9, P=0.9 and P=0.8). No pregnancy was observed in patients who had the interval between hysteroscopic polypectomy until ET less than 5days and the multivariable logistic regression analysis revealed that the interval between polyp resection and ET was significant predictor for live birth rate (odds ratio: 1.2, confidence interval: 1.01-1.5, P=0.04).For the management of the polyps less than 20mm which have been diagnosed during the stimulation phase, the performance of hysteroscopic polypectomy without cycle cancellation does not improve the pregnancy and live birth rates. Therefore, it seems that the continuation of the treatment cycle and ignorance of these polyps is the appropriate treatment choice and the performance of hysteroscopic polypectomy and frozen embryo transfer program could be the next treatment option.
- Effects of melatonin on oocyte maturation in PCOS mouse model. [JOURNAL ARTICLE]
- Anim Sci J 2016 Aug 17.
The purpose of oocyte in vitro maturation is generation of mature oocytes that could support future development. Efforts have been made to enhance oocyte developmental competence by developing optimal culture conditions. The present study is conducted to determine melatonin effects on quality of polycystic ovarian syndrome (PCOS) oocytes when it has been added during in vitro maturation, and immature oocytes were cultured in defined conditioned medium with and without different melatonin concentrations. Melatonin could significantly improve nuclear maturation of PCOS oocytes (81.1% vs. 56.3%, P < 0.05 were achieved with 10(-6) mol/L concentration). Cleavage rate was significantly higher in 10(-5) mol/L concentration compared to untreated oocytes in PCOS (54% vs. 35%, respectively) and it was significantly higher with 10(-6) mol/L concentration in the control group, 55% versus 38%, compared to untreated oocytes. This study showed that melatonin has the potential to induce oocyte nuclear maturation and guarantee fertilization potential.
- Fertility counseling and preservation practices in youth with lupus and vasculitis undergoing gonadotoxic therapy. [JOURNAL ARTICLE]
- Fertil Steril 2016 Aug 10.
To assess fertility counseling and preservation practices among children, adolescents, and young adults with rheumatic diseases undergoing cyclophosphamide (CTX) treatment.Retrospective chart review (2006-2016).Academic pediatric center.Male and female patients with systemic lupus erythematosus, Wegener's granulomatosis/granulomatosis with polyangiitis, or other vaculitides, receiving CTX treatment.None.Documentation of fertility counseling and fertility preservation.A total of 58 subjects met the inclusion criteria; 5 were excluded due to incomplete records, thus N = 53. Of these 75% were female (N = 40). Median age was 14 years at diagnosis and 15 years at first CTX treatment. A total of 51% of subjects (69% of males and 45% of females) had no documentation about potential fertility loss before CTX treatment. Among females where fertility counseling was documented, the only fertility preservation option discussed was leuprolide acetate (LA), which was pursued in all of these cases. Of 13 males (77% postpubertal), 3 were offered sperm banking, of whom 2 declined and the other attempted after treatment began and was azoospermic. Of 53 patients, 1 was referred to a fertility specialist. Mean cumulative CTX dose was 9.2 g in males and 8 g in females.Based on these findings, increasing awareness about infertility risk, fertility preservation options, and referral to fertility specialists is needed among pediatric rheumatologists. Prospective studies are needed to assess fertility outcomes in this patient population (including effectiveness of LA with regard to pregnancy rates [PRs]), as well as barriers/facilitators to fertility counseling and fertility preservation.
- Fresh versus Frozen Embryos for Infertility in the Polycystic Ovary Syndrome. [Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't]
- N Engl J Med 2016 Aug 11; 375(6):523-33.
The transfer of fresh embryos is generally preferred over the transfer of frozen embryos for in vitro fertilization (IVF), but some evidence suggests that frozen-embryo transfer may improve the live-birth rate and lower the rates of the ovarian hyperstimulation syndrome and pregnancy complications in women with the polycystic ovary syndrome.In this multicenter trial, we randomly assigned 1508 infertile women with the polycystic ovary syndrome who were undergoing their first IVF cycle to undergo either fresh-embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. After 3 days of embryo development, women underwent the transfer of up to two fresh or frozen embryos. The primary outcome was a live birth after the first embryo transfer.Frozen-embryo transfer resulted in a higher frequency of live birth after the first transfer than did fresh-embryo transfer (49.3% vs. 42.0%), for a rate ratio of 1.17 (95% confidence interval [CI], 1.05 to 1.31; P=0.004). Women who underwent frozen-embryo transfer also had a lower frequency of pregnancy loss (22.0% vs. 32.7%), for a rate ratio of 0.67 (95% CI, 0.54 to 0.83; P<0.001), and of the ovarian hyperstimulation syndrome (1.3% vs. 7.1%), for a rate ratio of 0.19 (95% CI, 0.10 to 0.37; P<0.001), but a higher frequency of preeclampsia (4.4% vs. 1.4%), for a rate ratio of 3.12 (95% CI, 1.26 to 7.73; P=0.009). There were no significant between-group differences in rates of other pregnancy and neonatal complications. There were five neonatal deaths in the frozen-embryo group and none in the fresh-embryo group (P=0.06).Among infertile women with the polycystic ovary syndrome, frozen-embryo transfer was associated with a higher rate of live birth, a lower risk of the ovarian hyperstimulation syndrome, and a higher risk of preeclampsia after the first transfer than was fresh-embryo transfer. (Funded by the National Basic Research Program of China and others; ClinicalTrials.gov number, NCT01841528.).
- A microdeletion at Xq22.2 implicates a glycine receptor GLRA4 involved in intellectual disability, behavioral problems and craniofacial anomalies. [Journal Article]
- BMC Neurol 2016.:132.
Among the 21 annotated genes at Xq22.2, PLP1 is the only known gene involved in Xq22.2 microdeletion and microduplication syndromes with intellectual disability. Using an atypical microdeletion, which does not encompass PLP1, we implicate a novel gene GLRA4 involved in intellectual disability, behavioral problems and craniofacial anomalies.We report a female patient (DGDP084) with a de novo Xq22.2 microdeletion of at least 110 kb presenting with intellectual disability, motor delay, behavioral problems and craniofacial anomalies. While her phenotypic features such as cognitive impairment and motor delay show overlap with Pelizaeus-Merzbacher disease (PMD) caused by PLP1 mutations at Xq22.2, this gene is not included in our patient's microdeletion and is not dysregulated by a position effect. Because the microdeletion encompasses only three genes, GLRA4, MORF4L2 and TCEAL1, we investigated their expression levels in various tissues by RT-qPCR and found that all three genes were highly expressed in whole human brain, fetal brain, cerebellum and hippocampus. When we examined the transcript levels of GLRA4, MORF4L2 as well as TCEAL1 in DGDP084's family, however, only GLRA4 transcripts were reduced in the female patient compared to her healthy mother. This suggests that GLRA4 is the plausible candidate gene for cognitive impairment, behavioral problems and craniofacial anomalies observed in DGDP084. Importantly, glycine receptors mediate inhibitory synaptic transmission in the brain stem as well as the spinal cord, and are known to be involved in syndromic intellectual disability.We hypothesize that GLRA4 is involved in intellectual disability, behavioral problems and craniofacial anomalies as the second gene identified for X-linked syndromic intellectual disability at Xq22.2. Additional point mutations or intragenic deletions of GLRA4 as well as functional studies are needed to further validate our hypothesis.
- Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann syndrome. [JOURNAL ARTICLE]
- Mol Cell Endocrinol 2016 Aug 5.:86-96.
The genetic basis is unknown for ∼60% of normosmic hypogonadotropic hypogonadism (nHH)/Kallmann syndrome (KS). DNAs from (17 male and 31 female) nHH/KS patients were analyzed by targeted next generation sequencing (NGS) of 261 genes involved in hypothalamic, pituitary, and/or olfactory pathways, or suggested by chromosome rearrangements. Selected variants were subjected to Sanger DNA sequencing, the gold standard. The frequency of Sanger-confirmed variants was determined using the ExAC database. Variants were classified as likely pathogenic (frameshift, nonsense, and splice site) or predicted pathogenic (nonsynonymous missense). Two novel FGFR1 mutations were identified, as were 18 new candidate genes including: AMN1, CCKBR, CRY1, CXCR4, FGF13, GAP43, GLI3, JAG1, NOS1, MASTL, NOTCH1, NRP2, PALM2, PDE3A, PLEKHA5, RD3, and TRAPPC9, and TSPAN11. Digenic and trigenic variants were found in 8/48 (16.7%) and 1/48 (2.1%) patients, respectively. NGS with confirmation by Sanger sequencing resulted in the identification of new causative FGFR1 gene mutations and suggested 18 new candidate genes in nHH/KS.
- Innate immunity and the sensing of infection, damage and danger in the female genital tract. [REVIEW, JOURNAL ARTICLE]
- J Reprod Immunol 2016 Jul 25.
Tissue homeostasis in the female genital tract is challenged by infection, damage, and even physiological events during reproductive cycles. We propose that the evolutionarily ancient system of innate immunity is sufficient to sense and respond to danger in the non-pregnant female genital tract. Innate immunity produces a rapidly inducible, non-specific response when cells sense danger. Here we provide a primer on innate immunity and discuss what is known about how danger signals are sensed in the endometrium and ovary, the impact of inflammatory responses on reproduction, and how endocrinology and innate immunity are integrated. Endometrial epithelial and stromal cells, and ovarian granulosa cells express pattern recognition receptors, similar to cells of the innate immune system. These pattern recognition receptors, such as the Toll-like receptors, bind pathogen-associated or damage-associated molecular patterns. Activation of pattern recognition receptors leads to inflammation, recruitment of immune cells from the peripheral circulation, and phagocytosis. Although the inflammatory response helps maintain or restore endometrial health, there may also be negative consequences for fertility, including perturbation of oocyte competence. The intensity of the inflammatory response reflects the balance between the level of danger and the systems that regulate innate immunity, including the endocrine environment. Understanding innate immunity is important because disease and inappropriate inflammatory responses in the endometrium or ovary cause infertility.
- Vitrification at Day3 stage appears not to affect the methylation status of H19/IGF2 differentially methylated region of in vitro produced human blastocysts. [JOURNAL ARTICLE]
- Cryobiology 2016 Aug 4.
One of the most widely used assisted reproductive technology (ART) is vitrification. The aim of this study is to evaluate DNA methylation of H19/IGF2 differentially methylation region (DMR) in in vitro produced human blastocysts derived from non-vitrified and vitrified day3 embryos. Day3 embryos derived from ICSI cycles from fertile couples referring for family balancing program were either biopsied or vitrified/warmed and subsequently biopsied. Following biopsy, embryos were cultured to day 5. Day5 blastocysts with desired sex were transferred or vitrified for future use. Blastocysts with un-desired sex were donated for research. The assessment of the embryos was performed in two non-vitrified and vitrified groups. Methylation level of H19/IGF2 DMR was analysed by bisulfite conversion and sequencing at 18 CpG sites (CpGs) located in this region. Results showed that the overall methylated CpGs percentages of this region in the vitrified and non-vitrified groups were 35.3% ± 3.6 and 38.27 ± 4.1%, respectively. The difference between the two groups was not significant. Vitrification of day3 embryo appears to have no adverse effect on DNA methylation status of H19/IGF2 DMR of embryos cultured in vitro to blastocyst stage. These data may have implications for performing frozen embryo cycles transfer instead of fresh embryo transfer cycles, owing to the naturally synchronized uterus and subsequently improved endometrial receptivity in frozen embryo transfer instead of imbalanced hormonal milieu in fresh embryo transfer cycles.
- Laparoscopic Anterior Resection with Transvaginal Specimen Extraction (TVSE) for Colorectal Cancer and Concomitant Total Hysterectomy and Bilateral Salpingo-Oophrectomy (THBSO): A Technical Description. [JOURNAL ARTICLE]
- Ann Surg Oncol 2016 Aug 5.
Natural orifice specimen extraction (NOSE) has evolved to circumvent the need for a specimen extraction site. Transvaginal specimen extraction (TVSE) for colorectal disease has been shown to be safe and feasible in selected cases.1 (,) 2 We describe our technique of TVSE in a case of laparoscopic ultra-low anterior resection (ULAR) with defunctioning ileostomy (DI) with a concomitant total hysterectomy and bilateral salpingo-oophrectomy (THBSO).A 74-year-old Chinese female was diagnosed with a mid-rectal cancer following colonoscopic evaluation for a change in bowel habits. Preoperative magnetic resonance imaging (MRI) suggested T2N0 disease and the patient was recommended for upfront surgery following multidisciplinary discussion. Computed tomography (CT) scan confirmed a 4.3 × 3.4 cm right adnexal cystic lesion, without enhancing septations or soft tissue component. No metastatic disease was identified. The patient underwent a laparoscopic ULAR with DI and THBSO with TVSE; operative time was 469 min. The specimen showed a 2.5 cm mid-rectal tumour. Histology revealed a pT3N1a moderately differentiated adenocarcinoma of the mid rectum, with 1 of 20 lymph nodes involved by metastatic carcinoma. The quality of the total mesorectal excision (TME) was good, with no breach in the mesorectal fascia. The distal and radial margins were 1.5 and 3.0 cm, respectively. The patient recovered well postoperatively, with minimal wound site pain, and was discharged well on postoperative day 5.TVSE is oncologically safe and feasible in certain malignant colorectal pathologies. It is an option to consider in selected cases that require a concomitant gynecological procedure.
- Cystic fibrosis transmembrane conductance regulator (CFTR) gene abnormalities in Indian males with congenital bilateral absence of vas deferens & renal anomalies. [Journal Article]
- Indian J Med Res 2016 May; 143(5):616-23.
The role of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in congenital bilateral absence of vas deferens and unilateral renal agenesis (CBAVD-URA) has been controversial. Here, we report the cases of five Indian males with CBAVD-URA. The objective was to evaluate the presence or absence of CFTR gene mutations and variants in CBAVD-URA. The female partners of these males were also screened for cystic fibrosis (CF) carrier status.Direct DNA sequencing of CFTR gene was carried out in five Indian infertile males having CBAVD-URA. Female partners (n=5) and healthy controls (n=32) were also screened.Three potential regulatory CFTR gene variants (c.1540A>G, c.2694T>G and c.4521G>A) were detected along with IVS8-5T mutation in three infertile males with CBAVD-URA. Five novel CFTR gene variants (c.621+91A>G, c.2752+106A>T, c.2751+85_88delTA, c.3120+529InsC and c.4375-69C>T), four potential regulatory CFTR gene variants (M470V, T854T, P1290P, Q1463Q) and seven previously reported CFTR gene variants (c.196+12T>C, c.875+40A>G, c.3041-71G>C, c.3271+42A>T, c.3272-93T>C, c.3500-140A>C and c.3601-65C>A) were detected in infertile men having CBAVD and renal anomalies Interpretation & conclusions: Based on our findings, we speculate that CBAVD-URA may also be attributed to CFTR gene mutations and can be considered as CFTR-related disorder (CFTR-RD). The CFTR gene mutation screening may be offered to CBAVD-URA men and their female partners undergoing ICSI. Further studies need to be done in a large sample to confirm the findings.