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Endocrinology AND Infertility, female [keywords]
- Obesity and reproductive function: a review of the evidence. [JOURNAL ARTICLE]
- Curr Opin Obstet Gynecol 2014 Sep 24.
Over the last decade, the evidence linking obesity to impaired reproductive function has grown. In this article, we review this evidence and discuss the underlying pathophysiology.Obese women are less likely than normal-weight women to achieve pregnancy. Female obesity adversely affects reproductive function through alterations in the hypothalamic-pituitary-ovarian axis, oocyte quality, and endometrial receptivity. It is unclear which mechanism contributes the most to subfecundity, and it is likely a cumulative process. Emerging data highlight the contribution of male obesity to impaired reproductive function and that couple obesity has synergistic adverse effects. Once pregnant, obese women are at higher risk for adverse pregnancy outcomes. Weight loss improves reproductive potential in obese patients. As obese women surpass 35 years of age, age may be more important than body mass index in determining reproductive potential.Obstetrician gynecologists need to be aware of the negative impact of obesity on reproductive function so that they appropriately counsel their patients. Further work is needed to clarify the underlying pathophysiology responsible for adverse effects of obesity on reproduction so that novel treatment approaches may be developed.
- Endometrial infusion of human chorionic gonadotropin at the time of blastocyst embryo transfer does not impact clinical outcomes: a randomized double-blind, placebo-controlled trial. [JOURNAL ARTICLE]
- Fertil Steril 2014 Sep 15.
To determine whether endometrial hCG infusion at the time of human blastocyst transfer impacts implantation rates.Randomized double-blinded placebo-controlled trial.Academic.Infertile couples with the female partner less than 43 years old (n = 300) undergoing fresh or frozen ET of one or two blastocysts.Patients undergoing ET were randomized into either a treatment or a control group. The treatment group received an infusion of 500 IU of hCG diluted in ET media. The control group received a sham infusion of ET media. Infusions were done using a separate catheter less than 3 minutes before actual ET.Sustained implantation rate: ongoing viable gestation (primary outcome) and ongoing pregnancy rate (secondary outcome).A total of 473 blastocysts were transferred into 300 patients. There were no differences between the two groups in sustained implantation rate (48.1% in the hCG group, 44.2% in the control group) or ongoing pregnancy rate (58.8% in the hCG group, 52.0% in the control group).Endometrial infusion of hCG at the time of blastocyst ET does not improve sustained implantation rates.NCT01643993.
- Comparison of the outcomes between reduced and nonreduced triplet pregnancies achieved by Assisted Reproductive Technology. [JOURNAL ARTICLE]
- Aust N Z J Obstet Gynaecol 2014 Sep 8.
In recent years, the significant increase in multiple pregnancies as a result of assisted reproductive techniques (ART) has introduced the concept of multifetal reduction techniques. However, it is still unclear whether there are significant advantages of using this technique.To compare the outcomes of triplet pregnancies achieved by ART managed expectantly with those receiving fetal reduction interventions.In this retrospective study of 115 triplet pregnancies, 57 pregnancies were reduced to twins while 58 were managed expectantly.The fetal loss rate before 24 weeks did not differ between reduced and nonreduced pregnancies (12.3% vs 12.1%). However, the results of those using fetal reduction techniques showed a lower incidence of preterm labour (26.3% vs 50%, P = 0.009), higher mean gestational age at delivery (35.1 ± 2.6 vs 32.4 ± 3.6 weeks, P = 0.002) and higher mean birthweights compared with the control group (2188 ± 547 vs 1674 ± 546 g, P < 0.001). The perinatal mortality rate was significantly lower in reduced triplets compared with those expectantly managed (6% vs 17.6%, P = 0.007). The rate of live birth was 94% in reduced and 82.4% in nonreduced pregnancies (P = 0.007). The percentages of neonates admitted to the neonatal intensive care unit (NICU) were 27.7 and 62.7% in reduced and nonreduced pregnancies, respectively (P < 0.001).In this observational cohort study reduction of triplets to twins decreased prematurity and increased birthweight without an increase in fetal loss. Additionally, there was a lower perinatal mortality, higher live birth rate and lower NICU admission.
- Time to pregnancy in subfertile women in German gynecological practices: analysis of a representative cohort of more than 60,000 patients. [JOURNAL ARTICLE]
- Arch Gynecol Obstet 2014 Sep 4.
The aim of this study was to assess the time from the first subfertility diagnosis to pregnancy (TTP) and to elucidate factors influencing TTP for patients in German gynecological practices comprising a representative sample and provide a realistic picture of the current situation in Germany.The study collective included all women with first-time diagnoses of female infertility (ICD: N97) or unfulfilled desire for children (ICD: Z31) from the representative database (IMS Disease Analyzer). Demographic data on patients such as their age (ranges 18-25, 26-30, 31-35, 36-40 or 51-50) and information on previous pregnancies and births and concomitant diseases were collected. Data pertaining to 61,815 women from 433 gynecological practices in Germany with a first diagnosis of female infertility or an unfulfilled desire for children were analyzed. The period of data collection was between January 1, 2001 to December 31, 2012 (=144 months). The mean observation period for the patients after the first gynecological consultation was 1,420 days (=47.3 months), with a standard deviation of 879 days.A total of 22,744 patients became pregnant during the first year of observation (36.8 %). The highest cumulative pregnancy rate was seen in women between 18 and 30 years of age (74.8 %). The older the women were, the lower the cumulative pregnancy rate became (18.1 % in the group of 41- to 50-year-old women). Cox regression calculations showed that the following factors considerably impaired the chances of pregnancy: age, endometriosis, diabetes mellitus, ovarian dysfunction, PCOS, previous infection of the genitourinary tract. In contrast, a couple of factors were proven to increase pregnancy rates, namely previous use of hormonal contraceptives, private insurance, previous birth, previous pregnancy and progesterone therapy (at any time).Along with information about reproductive physiology, such as decreasing fertility with maternal age, counseling in daily practice should also include individual factors influencing fertility. It is of the utmost importance to further increase public awareness of the impact of advanced female and male age on the reproductive outcome so that people can make well-informed decisions on when to start a family.
- Th17 cells and related cytokines in unexplained recurrent spontaneous miscarriage at the implantation window. [JOURNAL ARTICLE]
- Reprod Biomed Online 2014 Jul 10.
Unexplained recurrent spontaneous abortion (RSA) might be caused by the mother's immunological rejection of the fetus. In this cross-sectional study, the percentage of T helper 17 (Th17), T regulatory (Treg) cells and their cytokines as the main players of immunomodulation in peripheral blood lymphocytes during the luteal phase of 20 women with unexplained RSA were compared with 20 normal non-pregnant women. The percentage of Treg cells in the former was significantly lower compared with controls. The percentage of Th17 cells in the former was higher than controls. Expression of IL-23, IL-17, IL-6 cytokines in the former was significantly higher than controls, but the higher expression of IL-21 was not significant. The gene expression of TGF-β and FoxP3 in the former was lower than controls. Significant positive correlations were found between the percentage of Th17 cells with IL-23, IL-6 and IL-17 and between expression of IL-23 and IL-6 and IL-17. IL-6 gene expression showed a significant positive correlation with IL-17. Therefore, imbalance of Th17-Treg cells and the consequent changes in cytokine expression might be implicated in the pathogenesis of unexplained RSA and may provide new insight into the immunoregulatory events at the maternal-fetal interface.
- Gestational diabetes mellitus risk factors in women with polycystic ovary syndrome (PCOS). [JOURNAL ARTICLE]
- Eur J Obstet Gynecol Reprod Biol 2014 Aug 7.:195-199.
To compare the incidence of gestational diabetes mellitus (GDM) in Iranian infertile women with polycystic ovary syndrome (PCOS) and women without PCOS after pregnancies resulting from either assisted reproductive technology (ART) or spontaneous as well as to determine the risk factors of GDM in PCOS women.In a cross-sectional study, we evaluated medical records of 234 spontaneous pregnant women without PCOS in Akbarabadi Women's Hospital affiliated to Tehran University of Medical Science, Tehran, Iran, along with 234 pregnant women with PCOS and 234 pregnant non-PCOS women with ART conception who were treated at Royan institute, Tehran, Iran, at the same period of time, 2012 to February 2013. Exclusion criteria were as following: maternal age ≥40, family history of diabetes in first-degree relatives, pre-pregnancy diabetes and history of gestational diabetes, history of stillbirth, recurrent miscarriage, birth weight baby ≥4kg (macrosomia), parity >4, Cushing's syndrome, congenital adrenal hyperplasia and overt hypothyroidism. The GDM diagnosis was according to American Diabetes Association (ADA) criteria. Incidence and the risk factors for GDM were evaluated.The incidence rates of GDM were 44.4%, 29.9% and 7.3% for PCOS ART, non-PCOS ART and non-PCOS spontaneous pregnant women, respectively. Multivariable logistic regression was used for determining risk factors of GDM in PCOS women with adjusted odds ratios for age, parity and hypothyroidism, the results revealed the most important and significant predictors for development of GDM in PCOS women as follow: menstrual irregularity (OR=4.2; 95% CI=1.7-10.6), serum triglycerides level ≥150mg/dL (OR=1.9; 95% CI=1.07-3.6) and pregestational metformin use (OR=0.4; 95% CI=0.2-0.7).Pregnant Iranian women with a history of infertility and PCOS are at increased risk for developing GDM. It is recommendable to perform screening test for GDM in PCOS women with ART treatment, irregular menses and high serum triglycerides level in the early stage of pregnancy. Pregestational use of metformin can be effective in reducing the occurrence of GDM.
- Mayer-rokitansky-kuster-hauser syndrome associated with severe inferior vena cava stenosis. [Journal Article]
- Case Rep Obstet Gynecol 2014.:745658.
Precis. The postoperative course of a neovagina creation procedure in a young woman with Meyer-Rokitansky-Kuster-Hauser syndrome was complicated, despite prophylaxis, by extensive pelvic deep venous thrombosis secondary to unsuspected severe inferior vena cava stenosis.
Background.Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by congenital vaginal agenesis and an absent or rudimentary uterus in genotypical females. Malformations of the inferior vena cava (IVC) are not commonly associated with MRKH syndrome. We report a case of a patient with MRKH syndrome with severe IVC stenosis that was diagnosed when the patient presented with extensive pelvic deep venous thrombosis (DVT) during the postoperative course of a neovagina creation. Case. A 19-year-old female underwent a McIndoe procedure. Despite DVT prophylaxis, extensive pelvic DVT of the femoral vein was diagnosed on postoperative day 7. Therapeutic anticoagulation was initiated, and pharmacological and mechanical thrombolysis were performed. During these procedures, a hypoplastic IVC was noted.
Conclusion.MRKH syndrome can be associated with IVC malformations, which constitute an anatomical risk factor for postoperative DVT.
- VEGFR-1 blockade disrupts peri-implantation decidual angiogenesis and macrophage recruitment. [Journal Article]
- Vasc Cell 2014.:16.
Angiogenesis and macrophage recruitment to the uterus are key features of uterine decidualization; the progesterone-mediated uterine changes that allow for embryo implantation and initiation of pregnancy. In the current study, we characterized the expression of vascular endothelial growth factor receptor-1 (VEGFR-1) in macrophages and endothelial cells of the peri-implantation uterus and determined if VEGFR-1 function is required for decidual angiogenesis, macrophage recruitment, and/or the establishment of pregnancy.Expression of VEGFR-1 in uterine endothelial cells and macrophages was determined with immunohistochemistry. To assess the effect of continuous VEGFR-1 blockade, adult female mice were given VEGFR-1 blocking antibody, MF-1, every 3 days for 18 days. After 6 doses, females were mated and a final dose of MF-1 was given on embryonic day 3.5. Endothelial cells and macrophages were quantified on embryonic day 7.5. Pregnancy was analyzed on embryonic days 7.5 and 10.5.F4/80(+) macrophages are observed throughout the stroma and are abundant adjacent to the endometrial lumen and glands prior to embryo implantation and scatter throughout the decidua post implantation. VEGFR-1 expression is restricted to the uterine endothelial cells. F4/80(+) macrophages were often found adjacent to VEGFR-1(+) endothelial cells in the primary decidual zone. Continuous VEGFR-1 blockade correlates with a significant reduction in decidual vascular and macrophage density, but does not affect embryo implantation or maintenance of pregnancy up to embryonic day 10.5.We found that VEGFR-1 functions in both decidual angiogenesis and macrophage recruitment to the implantation site during pregnancy. VEGFR-1 is expressed by endothelial cells, however blocking VEGFR-1 function in endothelial cells results in reduced macrophage recruitment to the uterus. VEGFR-1 blockade did not compromise the establishment and/or maintenance of pregnancy.
- Toll-like receptors expression in follicular cells of patients with poor ovarian response. [Journal Article]
- Int J Fertil Steril 2014 Jul; 8(2):183-92.
Poor ovarian response (POR) to gonadotropin stimulation has led to a significant decline in success rate of fertility treatment. The immune system may play an important role in pathophysiology of POR by dysfunctions of cytokines and the growth factor network, and the presence of ovarian auto-antibodies. The aim of this study is to investigate the expression of toll-like receptors (TLR) 1, 2, 4, 5, 6 and cyclooxygenase (COX) 2 genes in follicular cells and concentration of interleukin (IL)-6, IL-8 and macrophage migration inhibitory factor (MIF), as major parts of innate immunity, in follicular fluid (FF) obtained from POR women in comparison with normal women.In this case-control study, 20 infertile POR patients and 20 normal women took part in this study and underwent controlled ovarian stimulation. The FF was obtained from the largest follicle (>18 mm). The FF was centrifuged and cellular pellet was then used for evaluation of expression of TLRs and COX2 genes by real-time PCR. FF was used for quantitative analysis for IL-6, IL-8 and MIF by enzyme-linked immunosorbent assay (ELISA).TLR1, 2, 4, 5, 6 and COX2 gene expression were significantly higher in POR (p<0.05). Concentration of IL-6, IL-8 and MIF proteins was significantly increased in POR compared with normal women (p<0.05).These findings support the hypothesis that the immune system may be involved in pathophysiology of POR through TLRs.
- Health-Related Quality of Life and Primi-Gravid: A Comparative Study of Natural Conception and Conception by Assisted Reproduction Technologies (ARTs). [Journal Article]
- Int J Fertil Steril 2014 Jul; 8(2):167-74.
Childbearing for the first time is a unique experience. Quality of life is an important indicator in health studies. This study aimed to assess the quality of life of women who were conceived by ARTs and had successful childbirth for the first time and to compare it with quality of life in women who become pregnant naturally and similarly had successful childbirth for the first time.This was a cross sectional comparative study. The accessible sam- ple was recruited from patients attending an infertility clinic and two obstetric and gynecology clinics in Tehran, Iran, during March 2010 to March 2011. In all 276 patients were approached. Of these, 162 women (76 women in natural conception group and 86 women in assisted reproduction technologies group) who met the inclusion criteria were entered into the study. Quality of life was assessed using the 36-item Short Form Health Survey (SF-36). Women completed the questionnaire at two time points: i. last trimester and ii. first month after delivery. Comparison was made between two groups using Mann-Whitney U test and paired samples t test.Comparing the SF-36 scores between women in natural conception group and ARTs group before childbirth, it was found that natural group had better condition on physical functioning, role limitation due to physical problems, bodily pain and social functioning, while the ARTs group reported better status on general health, vitality, role limitation due to emotional problems, and mental health. However, after childbirth, the ARTs group reported a better condition almost on all measures, except for physical functioning. Comparing differences in obtained scores between two groups before and after childbirth, the results showed that improvements in health related quality of life measures for the ARTs group were greater in all measures, expect for general health.The findings from this study suggest that health-related quality of life was improved in women who became a mother for the first time by either method. Comparing to women who became mother by natural conception, women who received ARTs showed better quality of life from this first successful experience.