Immunohistochemistry of Leukemia Inhibitory Factor and Integrin αVß3 in Mouse Endometrium Following Kisspeptin-54 Ovulation Trigger.

Kisspeptin (KP) is a group of hypothalamic neuropeptides encoded by KISS-1 gene. KP-54, a 54-amino-acid peptide, helps regulate the hypothalamic-pituitary-ovarian axis and plays a potential role in implantation. C57BL/6 J female mice were superovulated via intraperitoneal injection of 5 International Units (IU) pregnant mare serum gonadotrophin (day 1). Forty-eight hours later, mice (5/group) were injected with phosphate-buffered saline (PBS) (group A), 5 IU human chorionic gonadotrophin (hCG) (group B), or 3 nmol KP-54 (group C). On day 7, mice were euthanized and uteri excised to create paraformaldehyde-fixed paraffin-embedded sections that were immunostained for the implantation markers: leukemia inhibitory factor (LIF) and integrin αVß3 (ITG αVß3). Slides were scored for intensity of staining in endometrial glandular epithelium (GE) and stromal cells (SCs) via histoscore (H-score). Data were analyzed using the Kruskal-Wallis test followed by the Mann-Whitney U test for pairwise comparisons. LIF expression was significantly higher in GE and SCs of mice triggered with KP-54 compared to placebo (P = .009 for both), but only higher than hCG trigger group in SCs (P = .009). Meanwhile, ITG αVß3 expression was significantly higher in SCs of mice triggered with KP-54 compared to placebo (P = .028). In conclusion, using KP-54 as an ovulation trigger resulted in higher expression of the implantation markers LIF and ITG αVß3 in mice endometrium compared to hCG or placebo. This suggests a potential role for KP-54 trigger in improving embryo implantation in clinical IVF. However, further studies are needed to correlate these results with clinical implantation rates and pregnancy outcomes.

Immunoreactivity of Kisspeptin and Kisspeptin Receptor in Eutopic and Ectopic Endometrial Tissue of Women With and Without Endometriosis.

Endometriosis is characterized by the presence of ectopic endometrial tissues. Mechanisms of tissue dissemination in endometriosis may be similar to those involved in tumor metastasis. We hypothesize that dysregulation of kisspeptin (KISS1), a metastasis suppressor in endometrial carcinoma, may contribute to the pathogenesis of endometriosis. In this study, we characterized the immunoreactivity of kisspeptin and its receptor, KISS1R, in eutopic and ectopic endometrial tissue of women with and without endometriosis, in proliferative and secretory menstrual cycle phases. Immunohistochemistry was performed using KISS1 and KISS1R antibodies on samples from women with (n = 35) and without (n = 14) endometriosis. Samples from women with endometriosis included eutopic endometrium (n = 20) samples, superficial endometriotic implants (SUP, n = 10) deep infiltrating endometriotic implants (DIE, n = 15), and ovarian endometriomas (OMA, n = 15). Immunoreactivity was quantified using histoscores. KISS1 and KISS1R immunoreactivity was significantly lower in eutopic endometrial stroma of women with versus without endometriosis, regardless of the menstrual cycle phase (P = 0.001 and P = 0.015 respectively). In endometriotic implants, KISS1 levels were significantly lower in both glandular and stromal components of DIE (P < 0.01) and OMA (P < 0.01) compared to SUP. KISS1R immunoreactivity was lower in the glandular component of OMA (P = 0.035) compared to SUP. KISS1 and KISS1R levels are lower in eutopic endometrial stroma from women with versus without endometriosis, consistent with a role for decreased KISS1 expression in the pathogenesis of endometriosis. As deeply invasive lesions showed lower KISS1 levels than superficial lesions, downregulation of KISS1 levels may contribute to implant invasiveness.

Cytokines hold promise for human embryo culture in vitro: results of a randomized clinical trial.

OBJECTIVE: To evaluate the effects of cytokine enrichment of culture medium on embryological and clinical outcomes after intracytoplasmic sperm injection (ICSI). DESIGN: A randomized clinical trial. SETTING: In vitro fertilization centers. PATIENT(S): This trial included 443 ICSI cycles randomized into two groups. INTERVENTION(S): This study evaluated the influence of integration of granulocyte-macrophage colony-stimulating factor, heparin-binding epidermal growth factor-like growth factor, and leukemia inhibitory factor into culture media on human embryo development after ICSI. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate per a randomized participant. RESULT(S): Cytokine enrichment of culture medium showed improvement in ongoing pregnancy rate compared with no cytokines (106/224 [47%] vs. 78/219 [36%]; absolute rate difference [ARD] = 12; 95% confidence interval [CI], 2.5-21). This integration of cytokines also showed better rates of live birth (101/224 [45%] vs. 71/219 [33%]; ARD = 13; 95% CI, 4-21) and cumulative live birth (132/224 [60%] vs. 97/219 [44%]; ARD = 12; 95% CI, 4-20) and lower rate of pregnancy loss (27/124 [22%] vs. 37/103 [36%]; ARD = -14; 95% CI, -26 to -2) than conventional medium. Embryos developed in the cytokine-supplemented medium showed better blastocyst formation, quality, cryopreservation, and use than control medium. CONCLUSION(S): Integration of cytokines into human embryo culture media showed improvement in embryological and clinical outcomes after ICSI. However, the long-term effect of cytokine enrichment of a medium is still unclear and warrants further studies with longitudinal follow-up. CLINICAL TRIAL REGISTRATION NUMBER: NCT02420886 at ClinicalTrials.gov.

Artificial oocyte activation with SrCl2 or calcimycin after ICSI improves clinical and embryological outcomes compared with ICSI alone: results of a randomized clinical trial.

STUDY QUESTION: Are pregnancy and birth rates affected by artificial oocyte activation (AOA) with SrCl2 or calcimycin after ICSI for couples with male-factor infertility linked to abnormal sperm morphology or for couples with previous ICSI cycles of unexplained low fertilization or inadequate fertilization associated with impaired oocyte morphology? SUMMARY ANSWER: AOA with either SrCl2 or calcimycin can improve the rates of clinical pregnancy, ongoing pregnancy and live birth compared with ICSI alone, and the two agents have diverse effects for different subgroups of patients. WHAT IS KNOWN ALREADY: ICSI is a successful treatment for infertility, but not in all individuals. AOA has potential to overcome inadequate fertilization in ICSI. Calcimycin and SrCl2 are candidate agents for AOA, but their effectiveness remains to be compared. STUDY DESIGN, SIZE, DURATION: This study was a randomized, open-label, three-arm, parallel-group, double-centre, superiority trial conducted between April 2015 and January 2016. The study evaluated the effects of AOA with calcimycin or SrCl2 for clinical pregnancy rates after ICSI and included 343 couples divided into three groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples were included if they had two previous ICSI cycles of no or low fertilization (0-30%) with unknown causes or impaired oocyte morphology. Male-factor infertility cycles (frozen-thawed sperm, surgically retrieved sperm or ejaculates contained <10 millions spermatozoa/ml) undergoing their first ICSI attempt were also included if they had 100% abnormal sperm morphology (including globozoospermia and tapered-head). Couples were randomized to undergo ICSI with SrCl2 AOA, ICSI with calcimycin AOA or ICSI alone, with clinical pregnancy as the primary endpoint. Effect sizes were summarized as absolute rate differences (ARDs) and odds ratios (ORs), with precision evaluated by 95% CIs. MAIN RESULTS AND THE ROLE OF CHANCE: Both SrCl2 and calcimycin AOA improved clinical pregnancy rates compared to ICSI alone (49, 42 and 27%; ARD 22, 95% CI: 9-33; P = 0.0007 and ARD 16, 95% CI: 3-27; P = 0.014). SrCl2 and calcimycin AOA were also superior to ICSI alone on the rates of ongoing pregnancy (42, 36 and 23%; P = 0.0019 and P = 0.023) and live birth (40, 33 and 18%; P = 0.0002 and P = 0.012). Among couples with previous ICSI cycles of low fertilization, AOA with SrCl2 (but not with calcimycin) was superior to ICSI alone for rates of clinical pregnancy (ARD 35 percentage points (pp), P = 0.0007), ongoing pregnancy (ARD 27 pp, P = 0.009) and live birth (ARD 37 pp, P = 0.002). Among couples affected by male-factor infertility, AOA with calcimycin (but not with SrCl2) was superior to ICSI alone for rates of clinical pregnancy (ARD 22 pp, P = 0.006), ongoing pregnancy (ARD 19 pp, P = 0.013) and live birth (ARD 17 pp, P = 0.02). LIMITATIONS, REASONS FOR CAUTION: This study was an open-label trial, and this design might have introduced bias, although randomization methods were used. The study did not include a longitudinal follow-up, so further evidence is required to demonstrate the safety of AOA. WIDER IMPLICATIONS OF THE FINDINGS: The decision to use SrCl2 or calcimycin for AOA after ICSI may depend on whether the activation failure originates in the oocyte or the sperm. STUDY FUNDING/COMPETING INTEREST(S): The study received no funding and the authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NCT02424214. TRIAL REGISTRATION DATE: 22 April 2015. DATE OF FIRST PATIENT'S ENROLMENT: 27 April 2015.

Reproductive performance after conservative surgical treatment of postpartum hemorrhage.

OBJECTIVE: To evaluate the impact of bilateral internal iliac artery ligation (BIL), bilateral uterine artery ligation (BUAL), step-wise uterine devascularization (SWUD), and B-Lynch on infertility, ovarian reserve, and pregnancy outcome. METHODS: The study included 168 infertile or pregnant patients-recruited at outpatient clinics in Egypt-who had previously undergone uterine-sparing surgery (BIL [group I], n=59; SWUD [group II], n=65); BUAL [group III], n=2; and B-Lynch [group IV], n=42). One-way analysis of variance was used to compare the prevalence of infertility, the status of ovarian reserve, and the prevalence and type of relevant maternal and/or fetal obstetric complications between the groups. RESULTS: Groups II and IV had the highest prevalences of infertility. The ovarian reserve was significantly lower in group II. Unexplained infertility was the predominant cause of infertility in group I, anovulation and premature ovarian failure in group II, and endometriosis and intrauterine adhesions in group IV. The frequency of obstetric complications, particularly placenta previa and preterm labor, was high in group IV. CONCLUSION: Of the 4 procedures, BIL had the least deleterious effect on reproductive performance; SWUD increased the risk of premature ovarian failure, and B-Lynch increased the risks of endometriosis, intrauterine adhesions, placenta previa, and preterm labor.

Lower urinary tract symptoms following female genital mutilation.

OBJECTIVE: To estimate the prevalence of lower urinary tract symptoms (LUTS) following female genital mutilation (FGM). METHODS: A hospital-based, cross-sectional study was conducted from January 1, 2009, through January 1, 2012, at the urogynecology clinic of Sohag University Hospital. The participants were 251 women who had undergone different forms of FGM. RESULTS: A total of 251 women agreed to participate. All had the clitoris amputated, 7.1% had some form of mutilation to the labia majora, 33.8% had adhesions of the labia minora, 19.2% had clitoral retention cysts, and 38.8% reported at least 1 LUTS. Nocturia (38.6%) was the most prevalent LUTS, intermittency (23.5%) was the most prevalent voiding LUTS, and incomplete voiding (22.7%) was the most common post-micturition LUTS. All 3 types of LUTS were reported by 11.6% of the women. Those with Type II and Type III FGM had a significantly higher risk of having all 3 LUTS than those with Type I. CONCLUSION: Women with FGM are significantly more likely to have LUTS than women without FGM, and LUTS seem to be more burdensome in those with more extensive FGM.

Prognosis and determinants of pregnancy outcome among patients with post-hepatitis liver cirrhosis.

OBJECTIVE: To evaluate maternal, fetal, and neonatal outcomes and their associated risk factors among pregnant women with liver cirrhosis (LC). METHODS: A prospective cohort study was conducted at Sohag University Hospital, Egypt, between May 1, 2009, and April 1, 2012. Participants included 129 pregnant women with LC (study group), 647 pregnant women without LC (control group 1), and 853 non-pregnant women with LC (control group 2). Univariate and multivariate analyses were performed. RESULTS: Maternal, fetal, and neonatal complication rates were significantly higher in the study group than in control group 1 (P=0.001 for all complications). The rate of hepatic decompensation (HD) was higher in the study group than in control group 2 (63.6% vs 13.6%; P=0.001). Maternal mortality was higher in the study group (7.8%) than in either control group 1 (0.2%) or control group 2 (2.5%; P=0.001). Variceal bleeding during vaginal delivery was the most frequent cause of maternal mortality. Vaginal delivery and increasing gestational age were the key variables affecting the rate of HD (P=0.001 for both). CONCLUSION: The presence of LC during pregnancy was associated with high rates of maternal and neonatal complications. Increasing gestational age and vaginal delivery were the most important risk factors for HD.

Bee-honey and yogurt: a novel mixture for treating patients with vulvovaginal candidiasis during pregnancy.

OBJECTIVE: To evaluate the clinical and mycological cure rates of a novel mixture consisting of Bee-honey and yogurt compared to local antifungal agents for treating patients with vulvo-vaginal candidiasis (VVC) during pregnancy. MATERIALS AND METHODS: This is a prospective comparative study which included 129 patients with VVC during pregnancy. The participants were allocated into study group (n = 82) who received a mixture of Bee-honey and yogurt vaginally and control group (n = 47) who received local anti-fungal agents. The Chi-square test was used to evaluate the clinical and mycological cure rates and the side-effects of both modes of therapy. RESULTS: The clinical cure rate was significantly higher in the study than the control group (87.8 vs. 72.3%, respectively) while the mycological cure rate was higher in the control than the study group (91.5 vs. 76.9%, respectively). Both types of therapy were favorably tolerated by most of the patients. Side effects were reported only in 24.3 and 29.7% of patients in group I and II, respectively (p < 0.05). CONCLUSIONS: The mixture of Bee-honey and yogurt produced a high clinical cure rate and a reasonable mycological cure rate. It can be used as a complementary or an alternative to antifungal agents especially in patients with VVC during pregnancy.

Complications among adolescents using copper intrauterine contraceptive devices.

OBJECTIVE: To evaluate the rate and pattern of complications associated with use of the Copper T 380A intrauterine device (IUD) among adolescents. METHODS: A prospective comparative study of women eligible for IUD insertion who attended the family planning clinic of Sohag University Hospital, Egypt, between July 1, 2008 and December 31, 2010. The participants were categorized as adolescents or adults. The Copper T 380A IUD was inserted in all participants and follow-up visits were scheduled at 1, 3, and 6 months. Odds ratio and χ(2) square tests were used to compare the rates of complications at each visit. RESULTS: Of 1512 patients eligible for IUD insertion, 852 met the inclusion criteria: 281 adolescents and 571 adults. The rates of pain, bleeding, displacement, expulsion, and removal of IUDs were significantly higher in adolescents (P<0.05). The rates of these complications were high in adolescents younger than 16 years; the rates then decreased with age and became comparable with the adult rates at 18 years of age. CONCLUSIONS: IUD-associated complications were high in adolescents up to the age of 17 years. Our data suggest that adolescents younger than 18 years of age should be counseled carefully before IUD insertion, and examined more frequently to detect displacement or expulsion of the device.

Hydatid of Morgagni: a possible underestimated cause of unexplained infertility.

OBJECTIVE: To evaluate the possible role of hydatid of Morgagni in patients with unexplained infertility. STUDY DESIGN: This was a non-randomized controlled trial conducted at the Department of Obstetrics and Gynecology of Sohag University, Egypt. Two hundred and thirteen patients with unexplained infertility and hydatid of Morgagni diagnosed at laparoscopy were included. The laterality (bilateral vs unilateral), location (fimbrial vs juxta-fimbrial), number (single vs multiple) and diameter of the hydatids of Morgagni were recorded. Patients were allocated to a study group (n=127) who underwent laparoscopic excision of hydatid of Morgagni and a control group (n=86) who underwent no intervention. Patients were followed for six months without any infertility or hormonal treatment to detect spontaneous pregnancy. Patients missed during the follow-up or who received infertility treatment were excluded. Statistical analysis was done using Chi-square test and Student's t-test. To find the most important character of hydatid of Morgagni which impedes pregnancy, logistic regression analysis of the dependent variable (no pregnancy) and independent variables (different characters of hydatid of Morgagni) was carried out in the control group. RESULTS: Hydatid of Morgagni was detected in 52.1% of patients with unexplained infertility compared to 25.6% of those with explained infertility (p<0.001). The pregnancy rate was higher in the study group than the control group (58.7% vs 20.6%, p<0.001). The pregnancy rate was significantly higher in the study group than the control group if the hydatid cyst was bilateral (85.7% vs 5.3%, p<0.001), fimbrial (85.6% and 9.1%, p<0.001), single (57.6% and 30.3%, p<0.001) or 1-2 cm in diameter (58.1% and 25.5%, p<0.001). Logistic analysis showed that the bilaterality and fimbrial location of the hydatid of Morgagni were the most significant characteristics impeding pregnancy (odds ratio=7.27 and 3.67 respectively). CONCLUSIONS: Hydatid of Morgagni is a possible underestimated cause of unexplained infertility. Laparoscopic removal of hydatid of Morgagni in patients with unexplained infertility was followed with a high spontaneous pregnancy rate. This is particularly obvious with bilateral and fimbrial hydatid of Morgagni.

Female genital mutilation in Upper Egypt in the new millennium.

OBJECTIVE: To estimate the influence of the 2007 criminalization law on the prevalence and yearly incidence of female genital mutilation (FGM) in Upper Egypt and assess the attitudes of both the population and their health providers toward FGM. METHODS: Between September 15, 2008, and September 15, 2010, all girls and young women presenting at the Departments of Gynecology and Obstetrics or Pediatrics of Sohag and Qena University Hospitals were invited to answer a questionnaire, which was also presented to their parents. Another questionnaire was presented to all nurses, young physicians, and senior physicians working at either hospital. RESULTS: The prevalence of FGM was 89.2%. The incidence was 9.6% in 2000, began to decrease in 2006, and had reached 7.7% at the end of the study period in 2009 (P=0.05). In their vast majority, the procedures were performed by general practitioners. In total, 88.2%, 34.3% and 14.9% of nurses, young physicians, and senior physicians, respectively, approved the practice. CONCLUSION: The incidence of FGM is still very high in Upper Egypt in spite of the criminalization law. While general practitioners perform most procedures, most nurses are in favor of preserving the practice.

Adolescent pregnancy in Upper Egypt.

OBJECTIVE: To determine the reasons for adolescent pregnancy in Upper Egypt and to evaluate maternal, fetal, and neonatal outcomes. METHODS: All primigravidae under 30 years of age who attended the labor/delivery ward at Sohag University Hospital, Sohag, Egypt, between December 31, 2005, and December 31, 2009, were invited to participate. Participants were allocated to the study group (up to 19 years of age at first pregnancy) or the control group (20-30 years of age at first pregnancy). Maternal, obstetric, fetal, and neonatal complications were compared between the groups, and adolescent participants completed a questionnaire to identify the reasons for pregnancy. RESULTS: In total, 58.2% had married seeking motherhood. Rates of ectopic pregnancy, pre-eclampsia, eclampsia, premature rupture of membranes, preterm labor, and cesarean were significantly higher among adolescents younger than 15 years of age; the risk then decreased steadily with age and became comparable to the control group after 16 years of age. CONCLUSION: Adolescent pregnancy increases the risk of ectopic pregnancy, pre-eclampsia, eclampsia, premature rupture of membranes, preterm labor, and cesarean among mothers up to 16 years of age. After 16 years of age, pregnancy is not associated with increased risk of obstetric or neonatal complications.