Reproductive Sciences

The aim of this study was to evaluate the effects of exercise prior to or during pregnancy on maternal reproductive outcome, biochemical profile, and on fetal anomaly frequency in a rat pregnancy model utilizing chemically induced diabetes. Wistar rats (minimum n = 11 animals/group) were randomly assigned the following groups: group 1 (G1), sedentary, nondiabetic; G2, nondiabetic, exercised during pregnancy; G3, nondiabetic, exercised prior to and during pregnancy; G4, sedentary, diabetic; G5, diabetic, exercised during pregnancy; and G6, diabetic, exercised prior to and during pregnancy. A swimming program was utilized for moderate exercise. On day 21 of pregnancy, all rats were anesthetized to obtain blood for biochemical measurements. The gravid uterus was weighed with its contents, and the fetuses were analyzed. The nondiabetic rats exercised prior to pregnancy presented a reduced maternal weight gain. Besides, G2 and G3 groups showed decreased fetal weights at term pregnancy, indicating slight intrauterine growth restriction (IUGR). In the diabetic dams, the swimming program did not have antihyperglycemic effects. The exercise applied only during pregnancy caused severe IUGR, as confirmed by reduced fetal weight mean, fetal weight classification, and ossification sites. Nevertheless, exercise was not a teratogenic factor and improved the rats’ lipid profiles, demonstrating that the exercise presented possible benefits, but there are also risks prior and during pregnancy, especially in diabetic pregnant women.

Male infertility is a relatively common condition caused by low sperm production, immobile sperm, or blockages that prevent the delivery of sperm. This condition can be caused by a variety of illnesses, injuries, chronic health problems, lifestyle choices, other factors, or idiopathic, in which abnormal semen parameters occur without an identifiable cause. Medical management traditionally focuses on correcting endocrine abnormalities related to hormone deficiencies. Clomiphene citrate is an antiestrogen thought to increase sperm parameters in males attempting to conceive. The objective of this review was to evaluate the efficacy and safety of clomiphene citrate in the treatment of male patients with infertility. A literature search of MEDLINE (1966-June 2012) and EMBASE (1980-June 2012) was conducted using the medical terms clomiphene and male infertility and 9 clinical studies were identified. Overall, only 1 study detected a statistically significant benefit on the pregnancy rate in the clomiphene group; however, the majority of the studies demonstrated a statistically significant increase in sperm concentrations. At doses used to treat male infertility, clomiphene was well tolerated with no identified serious adverse effects. Based on the reviewed studies there is insufficient evidence to indicate that clomiphene is effective for the treatment of male infertility.

This study demonstrates a robust and thorough trial design leading to accurate and objective data collection. We recommend that future studies investigating heavy menstrual bleeding (HMB) should follow, and improve upon, this rigorous approach to menstrual trial data collection, not only to validate clinical results but also to improve the techniques used to acquire these results. We propose that the state-of-the-art methodology described here be used as the basis for new guidelines for the implementation of clinical trials in the area of HMB.

We did a double-blind, randomized, placebo-controlled study to assess the incidence of infectious complications and the protective effect of antibiotic administration during operative hysteroscopic procedures in an office setting. A total of 1046 consecutively enrolled women with intrauterine lesions were randomly allocated to the reference group (523 patients administered with 1 g of cefazolin intramuscularly) and the study group (523 patients administered with 10 mL of isotonic sodium chloride solution), and treated in office setting by operative hysteroscopy for endometrial polypectomy, uterine septa, submucosal myomas, and intrauterine adhesions. The primary outcome measure was the computation of difference between groups in postsurgical infectious complications occurring in the 5 days after the procedures. The time spent in performing the various procedures did not differ significantly (P > .05) between the groups. With respect to the overall rate of postsurgical infection, we found that 12 (1.15%) of 1046  patients referred with symptoms related to infective complications, 7 (1.3% of 523 women) in the study—untreated—group and 5 (1.0% of 523 women) in the reference group. Such incidences did not differ significantly between the groups (P > .05). Antibiotics were prescribed in all cases of postsurgical infection and the infective process resolved in few days. None of these patients developed serious infections with adnexal involvement, as confirmed by clinical and ultrasounds evaluation. The results of the current study would support the American College of Obstetricians and Gynecologists recommendation not to prescribe routine antibiotic administration in the case of hysteroscopic surgery.

We aimed to investigate whether the surgical removal of endometrioma alters the nuclear factor-kappa B1 (NF-kB1; p50/105) and NF-kB p65 (Rel A) expression in the eutopic endometrium of infertile women with endometrioma before and after laparoscopic removal of the ovarian endometrioma during the mid-secretory phase. Infertile women with endometrioma (n = 15) were enrolled. Infertile patients with nonendometriotic ovarian cyst (n = 10) and healthy fertile women (n = 10) were recruited as controls. Endometrial samples were obtained before and 3 months after the laparoscopic cystectomy. The NF-kB1 (p50/105) levels were analyzed by enzyme-linked immunosorbent assay (ELISA) in the endometrium of all groups before and after laparoscopic ovarian cystectomy during implantation window. Expression of NF-kB1 (p50/105) in eutopic endometrium was significantly higher in infertile women with endometrioma compared to nonendometriotic cyst and fertile controls (P < .05). Laparoscopic cystectomy resulted in a significant decrease in NF-kB1 expression in women with endometrioma. The NF-kB p65 (Rel A) immunoreactivity of eutopic endometrium decreased significantly subsequent to the surgical removal of the endometrioma. In conclusion, increased endometrial NF-kB expression may contribute to endometriosis-associated infertility.

Complete suppression of the production of sperm in rats with dienogest (DNG, 40 mg/kg body weight [bw]) plus testosterone undecanoate (TU, 25 mg/kg bw), every 45 days, was found to be associated with a significant increase in germ cell apoptosis. Caspase 3 activity and expression in testis were simultaneously upregulated. Rise in the activities of caspase 8 and 9 was associated with overexpression of upstream marker proteins from extrinsic (Fas [Fatty acid synthase], FasL [Fatty acid synthase ligand], and caspase 8) and intrinsic (Bax [Bcl2-associated-x protein], Bcl2 [B-cell lymphoma 2], and caspase 9) pathways of apoptosis. Apart from the germ cells, interstitial cell apoptosis was also observed along with a decline in the number of functional Leydig cells. It is therefore concluded that complete suppression of the production of sperm with DNG + TU is facilitated mainly through the removal of precursor germ cells through apoptosis. The process is largely modulated by upregulation of upstream and downstream marker proteins from intrinsic as well as extrinsic pathway of metazoan apoptosis.

Lactobacillus iners is prominent in the human vagina and is able to persist despite development of bacterial vaginosis and treatment with antibiotics. A probable factor in its persistent survival is its ability to be retained in the vaginal epithelia. Genome sequencing of the strain showed an organism deplete of many metabolic pathways, yet equipped with fibronectin (Fn)-binding adhesins. The objective of the present study was to assess the ability of L iners AB-1 to bind immobilized Fn. Results showed that the organism superiorly bound the protein compared to other species of Lactobacillus and known binders such as Staphylococcus aureus. Treatment of L iners cells by protease rendered its binding abilities to Fn nonfunctional. The findings indicate a mechanism of vaginal persistence for a Lactobacillus species, with implications for reproductive health.

The averaged incidences of nonsyndromal/isolated cleft lip (CL), cleft palate (CP), and cleft lip with cleft palate (CLCP) by each month-of-conception, and managed in our hospital in from 2002 to 2009 were correlated with the reported levels of sunshine, ultraviolet radiation, and ambient nitrogen oxides (nitrogen oxide, nitrogen monoxide, and nitrogen dioxide), sulfur dioxide, and ozone, at the month of, and then at 4 and 8 weeks after, conception. There were 25, 12, and 22 cases each of CL, CP, and CLCP, respectively, totaling 59 cases (1.21 of 1000 births). On regression analysis, sunshine correlated inversely with the isolated CL at (P = .009) 4 weeks (P = .005) and 8 weeks (P = .008) postconception, and with CP (P = .009) and CLCP (P < .001) at 8 weeks postconception, while NOx correlated inversely with CL (P = .018) and NO with CLCP (P = .031), at 8 weeks postconception. Our results suggested that the interaction between sunshine and nitrogen oxides with other factors results in the reported seasonal variation in the incidence of isolated oral-facial clefts.

Focal adhesions are integrin-rich microdomains that structurally link the cytoskeleton to the extracellular matrix and transmit mechanical signals. In the pregnant uterus, increases in integrin expression and activation are thought to be critical for the formation of the mechanical syncytium required for labor. The aim of this study was to determine which integrins are upregulated and localized to focal adhesions in pregnant human myometrium. We used quantitative polymerase chain reaction, Western blotting, and confocal microscopy to determine the expression levels and colocalization with focal adhesion proteins. We observed increases in several integrin transcripts in pregnant myometrium. At the protein level, integrins such as α₅-integrin (ITGA5), ITGA7, ITGAV, and ITGB3 were significantly increased during pregnancy. The integrins ITGA3, ITGA5, ITGA7, and ITGB1 colocalized with focal adhesion proteins in term human myometrium. These data suggest that integrins α3β1, α5β1, and α7β1 are the most likely candidates to transmit mechanical signals from the extracellular matrix through focal adhesions in pregnant human myometrium.

Rapid growth in infancy considerably increases the risk of obesity and metabolic disorders in adulthood especially among neonates born small. To investigate the mechanism involved, we developed an animal model of undernourishment in utero by maternal caloric restriction, in which the Z scores of body weight at weaning (19.5 days) positively correlated with parameters of obesity, metabolic disorders, and remodeling of subcutaneous adipose tissue, such as numbers of macrophages in adipose tissue, the ratio of inflammatory M1 to anti-inflammatory M2 macrophages, estimated by gene expression of specific antigens, and the relative ratio of small adipocytes less than 30 μm in diameter, on a high-fat diet at 17 weeks of age. To our knowledge, this is the first report of a possible connection between infantile body weight and adipose tissue remodeling in obesity after undernourishment in utero.

Innate and adaptive immune cells secrete different cytokines, which participate through distinct mechanisms in cell-mediated immunity and humoral immune responses. The aim of this study was to evaluate the immune response through analysis of type 1 (Th1), Th2, and Th17 cells in patients with epithelial ovarian cancer (EOC). Our study included 44 patients with EOC (study group) and 32 gynecological patients with no ovarian disease (control group). Fragments of ovarian tissue and blood samples were collected in both groups and aliquots of intracystic fluid and peritoneal fluid were recovered from the EOC patient group. Interleukin (IL)-2/IL-4/IL-6/IL-10/IL-17/tumor necrosis factor (TNF)-α/interferon (IFN)-γ levels were measured by cytometric bead array. Statistical analysis included chi-squared, Student t, Mann-Whitney, Kruskal-Wallis tests, and Cox regression model. Patients with EOC were associated with higher levels of TNF-α/IL-4/IL-6/IL-10 compared to the control group. Both IL-10 and TNF-α concentrations were higher in patients with stage III/IV EOC and also associated with higher levels of cancer antigen 125. Higher Th1-mediated immune response was observed when the cytoreduction was considered optimal. However, patients with EOC with unsatisfactory cytoreductive surgery and undifferentiated tumors were associated with higher concentrations of Th2 cytokines in the 4 sites studied. Higher IL-6/IL-10 and lower IFN-γ concentrations were also associated with a lower overall survival rate in patients with EOC. The EOC group presented a predominantly Th2 response and an immunosuppressant standard and had association between IL-6/IL-10/IFN-γ and prognosis.