Young Women Of Reproductive Age Research Articles

Reproductive function in patients with malignant ovarian germ cell tumours

Malignant ovarian germ cell tumors (MOGCT) generally affect young women. The optimal volume of surgical treatment is unilateral adnexectomy. BEP-regimen chemotherapy (ChT) is the most effective regimen of treatment. Since this disease affects mainly adolescents and young women of reproductive age, one of the most important priorities concerning this category of patients is the fertility preservation. The aim of this study was analysis of long-term effects of ChT on reproductive function in a large population of young women treated for MOGCT in our center. Materials and methods. Inclusion criteria in our study were MOGCT, fertility-sparing surgery, cisplatin- and etoposide-based induction ChT (BEP/EP regimen), age 16-49 years. Presence of menstruation before treatment; no relapse following ChT at least 1 year. Blood tests were taken for hormones of ovarian function (follicle-stimulating hormone, luteinizing hormone, estradiol, anti-Mullerian hormone (AMH), inhibin B) to assess their menstrual, reproductive function, post therapeutic status of pregnancy or delivery. Results. The median time from the end of ChT until the date of filling out the questionnaire was 90 months (12–228 months). 58 (93.5%) of the 62 patients received BEP/EP regimen as a first line treatment, 4 (6.5%) treated with other regimens. During the ChT 42 (71.2%) patients developed amenorrhea due to the toxic effect of ChT. Among 47 women with regular menstruation after completion of ChT 23/47 (49%) patients attempted conception, 18/23 (78.3%) women conceived, 20 live birth deliveries were received. Correspondingly there were 2/18 (11%) miscarriages and 6/18 (33.3%) terminations. Four women were pregnant at the moment of the analysis. Inhibin B level was normal in all 15 evaluated pts (median 74,4 pg/ml, range 10–120). Median of AMH level was 0,97 ng/ml (range 0.08-6). In 10 (52.6%) of 19 pts AMH level was < 1 ng/ml, that was considered a decrease of ovarian reserve.

Influence of reproductive behavioral norms on the demographic situation of the Republic of Srpska

Since the origin of mankind, society is facing two major problems regarding subsistence of human population; birth and its control. Low reproductive norms could not be avoided in any modern society, and therefore the circumstances on our localities did not record positive changes in the system of increased birth, as well as in stimulation of young women in reproductive age to contribute the demographic recovery of the country, on the individual level. We are facing with the fact that the economic cost of parenting is increasing in line with the modern system of social values which in terms of depopulation can be very unfavorable for the survival of future generations. Besides economic instability, low reproductive norms are affected by incompatibility of work and parenting, lack of free time for child care, short time of maternity leave, the size of housing, unemployment and many other factors. According to Glas, children should be bought by the actual price, considering that is necessary to reduce the economic cost of parenthood. The research was based on the questionnaire, which was consisted of questions regarding the level of informing on demographic situation in the Republic of Srpska, birth control methods, the most commonly used methods, what is the current and optimal number of children they wish to have, and whether, is there a measure which could contribute to the solution of reproductive problems. The survey was conducted on the women in reproductive age, up to 40 years old.

Combined hormonal contraception and the risk of venous thromboembolism: a guideline

While venous thromboembolism (VTE) is rare in young women of reproductive age, combined oral contraceptives increase the risk of VTE. In the patient in whom combined hormonal contraception is appropriate, it is reasonable to use any currently available preparation.

Impact of chemotherapy on androgen and follicular measures of ovarian reserve in female cancer survivors

Future fertility is an important concern for many cancer survivors. Androgen production is necessary for the development of competent follicles and for long term sexual health and well-being. However, the effects of chemotherapy on androgen production have not been examined. This study sought to identify factors associated with circulating androgen levels during and immediately after cancer therapy in young reproductive-aged women.

A multicentre, open-label, randomised phase III study comparing a new levonorgestrel intrauterine contraceptive system (LNG-IUS 8) with combined oral contraception in young women of reproductive age

Objectives: To compare user satisfaction and adverse events (AEs) with a levonorgestrel intrauterine system (LNG-IUS 8; average levonorgestrel release rate approximately 8 μg/24 h over the first year [total content 13.5 mg]) and a 30 μg ethinyl estradiol/3 mg drospirenone (EE/DRSP) combined oral contraceptive (COC) in a population of young women.Methods: Nulliparous and parous women (aged 18–29 years) with regular menstrual cycles (21–35 days) were randomised to LNG-IUS 8 or EE/DRSP for 18 months. The primary endpoint was the overall user satisfaction rate at month 18/end of study visit.Results: Overall, 279 women were randomised to LNG-IUS 8 with attempted placement and 281 women were randomised to EE/DRSP and took ≥1 pill; the mean age was 23.7 and 23.9 years, and 77.4% and 73.3% were nulliparous, respectively. At month 18/end of study, 82.1% and 81.9% of women, respectively, reported being ‘very satisfied’ or ‘satisfied’ with their treatment; however, significantly more LNG-IUS 8 users reported a preference to continue their treatment post-study (66.2% vs 48.8%; p = 0.0001). There were two pregnancies (one ectopic pregnancy, one spontaneous abortion) reported in the LNG-IUS 8 group and six (three live births, two spontaneous abortions, one induced abortion) in the EE/DRSP group.Conclusions: LNG-IUS 8 and EE/DRSP were associated with similarly high user satisfaction rates. However, LNG-IUS 8 users were significantly more likely to prefer to continue their contraceptive method post-study, indicating that a levonorgestrel intrauterine system is an appealing contraceptive option for young women.

A survey on fertility management in young women of reproductive age treated with chemotherapy.

Treatment-related infertility is an important issue for cancer survivors of reproductive age. We aimed to determine the understanding and management of fertility issues in cancer survivors by health care providers. We studied 112 patients aged 15-40years who underwent chemotherapy in Tokushima University Hospital. The gynecologists and oncologists who treated these patients were surveyed regarding their concerns about infertility issues in young cancer survivors. Of the 112 women studied, 57 had iatrogenic amenorrhea. Five were referred to reproductive specialists before or during treatment. Three patients with breast cancer were referred after treatment; they could not undergo fertility treatment due to ovarian failure after chemotherapy. Forty-five medical doctors answered the survey: 21 gynecologists (including 9 fertility specialists), 13 oncologists, and 11 surgeons. Of the oncologists and surgeons, 37.5% (9/24) referred their patients to fertility experts. They listed certain issues regarding the patients: (1) anxiety that the intervention will alter the prognosis by delaying cancer treatment, and (2) a lack of communication between the oncologist and the fertility specialist. Almost all physicians agreed that fertility counseling was needed before chemotherapy. This report showed the importance of oncofertility counseling and cooperation between oncologists and fertility specialists. Fertility in cancer survivors depends on type of cancer treatment applied, chemotherapy regimen, and age at treatment. Our institute is now equipped for oncofertility counseling and refers patients for fertility preservation prior to cancer treatment.

Maternal marijuana use has independent effects on risk for spontaneous preterm birth but not other common late pregnancy complications.

Widespread legalisation of marijuana raises safety concerns for its use in pregnancy. This study investigated the association of marijuana use prior to and during pregnancy with pregnancy outcomes in a prospective cohort of 5588 nulliparous women from the international SCOPE study. Women were assessed at 15±1 and 20±1 weeks' gestation. Cases [278 Preeclampsia, 470 gestational hypertension, 633 small-for-gestational-age, 236 spontaneous preterm births (SPTB), 143 gestational diabetes] were compared separately with 4114 non-cases. Although the numbers are small, continued maternal marijuana use at 20 weeks' gestation was associated with SPTB independent of cigarette smoking status [adj OR 2.28 (95% CI:1.45-3.59)] and socioeconomic index (SEI) [adj OR 2.17 (95% CI:1.41-3.34)]. When adjusted for maternal age, cigarette smoking, alcohol and SEI, continued maternal marijuana use at 20 weeks' gestation had a greater effect size [adj OR 5.44 (95% CI 2.44-12.11)]. Our data indicate that increasing use of marijuana among young women of reproductive age is a major public health concern.

Novel correlates between antimüllerian hormone and menstrual cycle characteristics in African-American women (23–35 years-old)

To characterize normative antimüllerian hormone (AMH) levels and ascertain which factors are associated with AMH inalarge cohort of reproductive-age women. Cross-sectional study. Not applicable. A total of 1,654 African-American women (AAW) ages 23-34 at recruitment. Not applicable. Serum AMH measured using an ultrasensitive ELISA. The median AMH was 3.18ng/mL, and there was a significant, but nonlinear, relationship between age and AMH, with levels peaking at age 25. As AMH was not normally distributed, log transformation was performed and used for all analyses. In a multivariable age-adjusted model, body mass index, current use of hormonal contraception, and history of a thyroid condition were inversely associated with AMH, while history of abnormal menstrual bleeding and menstrual cycles longer than 35days were positively associated with AMH. While age is correlated with AMH, it accounts for only a portion of the variation seen. This study adds valuable information to the existing literature on normative AMH levels in young reproductive-age women. While our findings fill a critical data gap for ovarian reserve in AAW, the insights gained will be of benefit for all women.

Surgical treatment of deep infiltrating rectal endometriosis: in favor of less aggressive surgery

Deep infiltrating endometriosis of the rectum is a severe disease concerning young women of reproductive age. Because it is a benign condition, aggressive surgical treatment and subsequent complications are not always accepted by young patients. Two surgical approaches exist: the radical approach, employing colorectal resection; and the conservative approach, based on rectal shaving or full-thickness disc excision. At present, the majority of patients with rectal endometriosis worldwide are managed by the radical approach. Conversely, as high as 66% of patients with colorectal endometriosis can be managed by either rectal shaving or full-thickness disc excision. Most arguments that used to support the large use of the radical approach may now be disputed. The presumed higher risk of recurrence related to conservative surgery can be balanced by a supposed higher risk of postoperative bowel dysfunction related to the radical approach. Bowel occult microscopic endometriosis renders debatable the hypothesis that more aggressive surgery can definitively cure endometriosis. Although most surgeons consider that radical surgery is unavoidable in patients with rectal nodules responsible for digestive stenosis, conservative surgery can be successfully performed in a majority of cases. In multifocal bowel endometriosis, multiple conservative procedures may be proposed, provided that the nodules are separated by segments of healthy bowel of longer than 5 cm. Attempting conservation of a maximum length of rectum may reduce the risk of postoperative anterior rectal resection syndrome and subsequent debilitating bowel dysfunction and impaired quality of life. Promotion of less aggressive surgery with an aim to better spare organ function has become a general tendency in both oncologic and benign pathologies; thus the management of deep colorectal endometriosis should logically be concerned, too.

Oral follicle-stimulating hormone agonist tested in healthy young women of reproductive age failed to demonstrate effect on follicular development but affected thyroid function

To assess the safety, pharmacokinetics, and pharmacodynamics of MK-8389. Double-blind, placebo-controlled, parallel-group, ascending dose study. Two clinical research organizations. Healthy young women. Once-daily oral doses of MK-8389 or placebo for 14days. Safety, including thyroid function tests (TFTs), pharmacokinetics, and follicular development (follicle size and number and serum E2 and inhibin B levels). Treatment with MK-8389 was generally safe and well tolerated. An effect on TFTs was observed, which was transient and did not lead to clinical signs or symptoms but prevented dose escalation above 40mg. MK-8389 was rapidly absorbed, slowly eliminated, and showed a large peak-to-trough ratio. No clinically meaningful effect was seen on follicle size and numbers, which was consistent with the low E2 levels. At doses >20mg, inhibin B levels were increased, suggesting early follicular development at higher doses. Oral administration of MK-8389 demonstrated acceptable systemic exposure and was generally well tolerated. This study failed to demonstrate a clinically meaningful effect of MK-8389 on follicular development, whereas MK-8389 unexpectedly affected thyroid function. This study did not explore doses above 40mg given the changes observed in TFTs, which may relate to high MK-8389 peak concentrations. EudraCT Number 2010-022396-57.

MG-119 Genetic polymorphism in the vitamin D receptor gene and 25-hydroxyvitamin D serum levels in east indian women with polycystic ovary syndrome

<h3>Background</h3> Polycystic ovary syndrome (PCOS) is the most common metabolic abnormality such as changes in lipid profile, diabetes, hypertension and metabolic syndrome occurring in young women of reproductive age. Low vitamin D levels were found to be associated with the development of obesity and insulin resistance in women with PCOS. Variants on vitamin D receptor (VDR) gene have also been related to metabolic comorbidities in general population. <h3>Aim</h3> The aim of this case-control study was to investigate whether the VDR gene polymorphisms are associated with susceptibility to PCOS. <h3>Methods</h3> Women with PCOS and a control group, all aged 16–40 years, were enrolled. Genotyping of VDR Fok-I (rs2228570), VDR Apa-I (rs7975232) as well as GC (rs2282679), DHCR7 (rs12785878) SNPs between groups were determined by using direct sequencing. Serum 25-hydroxyvitamin D [25(OH)] levels were measured by ELISA. <h3>Results</h3> Mean serum 25(OH)D in the PCOS and control samples were 19.08 ± 7 and 23.27 ± 6.03 (p = 0.048) which were significantly lower in PCOS patients compared with controls. CC genotype of the VDR Apa-I SNP was same frequent in PCOS (25.6%) and controls (25.6%) (OR: 0.9995; 95% CI: 0.528 to 1.8921; p = 0.9987). The CC genotype was also significantly associated with both lower E2 (p = 0.031) and Androstenedione levels (p = 0.062). We observed a significant association of GC polymorphism with 25(OH)D levels. PCOS women carrying the GG genotype (in GC genes) had significantly higher risk for vitamin D deficiency than women carrying the TT genotype. <h3>Conclusions</h3> In conclusion, data from this study indicate that vitamin D levels are lower, and vitamin D deficiency more frequent, in PCOS than in controls. The present findings suggest that the Apa-I, Fok-I polymorphism of the VDR gene is associated with PCOS and seems to modulate ovarian steroid secretion. Further studies are needed to better clarify the biological mechanisms by which the polymorphism influences PCOS risk.

Fertility and early pregnancy outcomes after conservative treatment for cervical intraepithelial neoplasia.

Cervical intra-epithelial neoplasia (CIN) typically occurs in young women of reproductive age. Although several studies have reported the impact that cervical conservative treatment may have on obstetric outcomes, there is much less evidence for fertility and early pregnancy outcomes. To assess the effect of cervical treatment for CIN (excisional or ablative) on fertility and early pregnancy outcomes. We searched in January 2015 the following databases: the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library, Issue 12, 2014), MEDLINE (up to November week 3, 2014) and EMBASE (up to week 52, 2014). We included all studies reporting on fertility and early pregnancy outcomes (less than 24 weeks of gestation) in women with a history of CIN treatment (excisional or ablative) as compared to women that had not received treatment. Studies were classified according to the treatment method used and the fertility or early pregnancy endpoint. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effects model and inter-study heterogeneity was assessed with I(2). Two review authors (MK, AM) independently assessed the eligibility of retrieved papers and risk of bias. The two review authors then compared their results and any disagreements were resolved by discussion. If still unresolved, a third review author (MA) was involved until consensus was reached. Fifteen studies (2,223,592 participants - 25,008 treated and 2,198,584 untreated) that fulfilled the inclusion criteria for this review were identified from the literature search. The meta-analysis demonstrated that treatment for CIN did not adversely affect the chances of conception. The overall pregnancy rate was higher for treated (43%) versus untreated women (38%; RR 1.29, 95% CI 1.02 to 1.64; 4 studies, 38,050 participants, very low quality), although the inter-study heterogeneity was considerable (P < 0.01). The pregnancy rates in treated and untreated women with an intention to conceive (88% versus 95%, RR 0.93, 95% CI 0.80 to 1.08; 2 studies, 70 participants, very low quality) and the number of women requiring more than 12 months to conceive (14% versus 9%, RR 1.45, 95% CI 0.89 to 2.37; 3 studies, 1348 participants, very low quality) were no different. Although the total miscarriage rate (4.6% versus 2.8%, RR 1.04, 95% CI 0.90 to 1.21; 10 studies, 39,504 participants, low quality) and first trimester miscarriage rate (9.8% versus 8.4%, RR 1.16, 95% CI 0.80 to 1.69, 4 studies, 1103 participants, low quality) was similar for treated and untreated women, CIN treatment was associated with an increased risk of second trimester miscarriage, (1.6% versus 0.4%, RR 2.60, 95% CI 1.45 to 4.67; 8 studies, 2,182,268 participants, low quality). The number of ectopic pregnancies (1.6% versus 0.8%, RR 1.89, 95% CI 1.50 to 2.39; 6 studies, 38,193 participants, low quality) and terminations (12.2% versus 7.4%, RR 1.71, 95% CI 1.31 to 2.22; 7 studies, 38,208 participants, low quality) were also higher in treated women.The results should be interpreted with caution. The included studies were often small with heterogenous design. Most of these studies were retrospective and of low or very low quality (GRADE assessment) and were therefore prone to bias. Subgroup analyses for the individual treatment methods and comparison groups and analysis to stratify for the cone length was not possible. This meta-analysis suggests that treatment for CIN does not adversely affect fertility, although treatment was associated with an increased risk of miscarriage in the second trimester. These results should be interpreted with caution as the included studies were non-randomised and many were of low or very low quality and therefore at high risk of bias. Research should explore mechanisms that may explain the increase in mid-trimester miscarriage risk and stratify this impact of treatment by the length of the cone and the treatment method used.

European Society of Gynecological Oncology Task Force for Fertility Preservation: Clinical Recommendations for Fertility-Sparing Management in Young Endometrial Cancer Patients.

Endometrial cancer (EC) in young women of reproductive age is a relatively rare diagnosis. However, since in the modern era women delay their childbearing for a variety of social reasons, more and more women in the near future will be nulliparous and have a diagnosis of EC at the same time. Hence, a more conservative approach of EC is desirable to preserve fertility of these women, without compromising their survival. Recently, the number of studies reporting encouraging results on fertility-sparing management of EC with high dose of progestins is increasing. It seems that preserving the uterus and the ovaries in a carefully selected patient with EC confers only a very small risk combined with an enormous benefit. Selection of women suitable for such a conservative approach, as well as method of treatment, follow-up, recurrence, obstetric outcomes, and survival rates are very important parameters when consulting women with EC wishing to preserve their fertility. In this article, we try to elucidate all the previously mentioned aspects and formulate clinical recommendations, based on published data, about the most proper approach and consultation of these patients.

The Contribution of Cervicovaginal Infections to the Immunomodulatory Effects of Hormonal Contraception.

ABSTRACTParticular types of hormonal contraceptives (HCs) and genital tract infections have been independently associated with risk of HIV-1 acquisition. We examined whether immunity in women using injectable depot medroxyprogesterone acetate (DMPA), combined oral contraceptives (COC), or no HCs differs by the presence of cervicovaginal infections. Immune mediators were quantified in cervical swabs from 832 HIV-uninfected reproductive-age Ugandans and Zimbabweans. Bacterial infections and HIV were diagnosed by PCR, genital herpes serostatus by enzyme-linked immunosorbent assay (ELISA), altered microflora by Nugent score, and Trichomonas vaginalis and Candida albicans infection by wet mount. Generalized linear models utilizing Box-Cox-Power transformation examined associations between levels of mediators, infection status, and HCs. In no-HC users, T. vaginalis was associated with broadest spectrum of aberrant immunity (higher interleukin 1β [IL-1β], IL-8, macrophage inflammatory protein 3α [MIP-3α], β-defensin 2 [BD2], and IL-1 receptor antigen [IL-1RA]). In women with a normal Nugent score and no genital infection, compared to the no-HC group, COC users showed higher levels of IL-1β, IL-6, IL-8, and IL-1RA, while DMPA users showed higher levels of RANTES and lower levels of BD2, both associated with HIV seroconversion. These effects of COC were blunted in the presence of gonorrhea, chlamydia, trichomoniasis, candidiasis, and an abnormal Nugent score; however, RANTES was increased among COC users with herpes, chlamydia, and abnormal Nugent scores. The effect of DMPA was exacerbated by lower levels of IL-1RA in gonorrhea, chlamydia, or herpes, SLPI in gonorrhea, and IL-1β, MIP-3α, and IL-1RA/IL1β ratio in trichomoniasis. Thus, the effects of HC on cervical immunity depend on the genital tract microenvironment, and a weakened mucosal barrier against HIV may be a combined resultant of genital tract infections and HC use.

Use of Optimization Modeling for Selecting National Micronutrient Intervention Strategies: An Example Based on Potential Programs for Control of Vitamin A Deficiency in Cameroon.

Vitamin and mineral (micronutrient [MN]) deficiencies are common in lower income countries, especially among young children and women of reproductive age. These deficiencies are cause for serious concern because of their high prevalence and their associated complications, which include depressed immune function and increased risk and severity of infections, impaired neurocognitive development, and anemia, which together result in elevated mortality and reduced human productive capacity. A broad range of different intervention strategies are available to control MN deficiencies. At present, these interventions are usually implemented at a national scale through different public and private sector entities, often with little coordination. We have developed a set of models based on the estimated ability of different interventions to achieve effective coverage and the necessary financial resources required to deploy these interventions. The models provide a unified and transparent framework for considering different options using the common indicator of effective coverage. More specifically, information on nutritional benefits and costs are analyzed using an economic optimization model to identify the mix of interventions that could be delivered to specific target groups in particular geographic areas to achieve a desired level of effective coverage at lowest cost. Alternatively, these optimization models can be developed to identify the combination of interventions needed to achieve the maximum effective coverage, given specified budgetary limitations. The results of these models can be useful input into policy-making processes. To introduce this analytical approach, the set of papers in this volume addresses the problem of vitamin A deficiency among young children in Cameroon.

Third Grade Uterine Prolapse in Young Age after Second Surgical Reconstruction

Recurrent Pelvic organ prolapse is a condition that affects the quality of life for women. Uterine prolapse percentage reached 35-50 % of women and the incidence increases with age and parity. In young women in reproductive age, uterine prolapse incidence is low, only 2 % nulliparous women experience POP. This case report aims to study the causes of uterine prolapse stage III-IV at young age after second reconstructive surgery. A 38 years old woman came to gynecology outpatient clinic dr Soetomo hospital, her chief complaint was uterine dropped after second reconstructive surgery. She had the first surgery at the age of 22, with reduction of round ligament (Baldy-Webster suspension), and had the second reconstruction surgery at the age of 31 years. A Purandare procedure was done few weeks afterwards, when she had cough and the pelvic organ going downward again. The third operation is scheduled, few weeks afterward, it was decided to do purandare procedure because of her age and nulliparity. However, due to severe adhesion and during surgery right tuboovarial abcess is found, SVH-SOD, adhesiolisis and Purandare procedure to suspend cervix stomp. Histopathologic result shows decreased collagen levels IA2. As a conclusion, the cause of twice uterine prolapse in these patients is the decrease of collagen, intraabdominal pressure and infection from tuboovarial abscess.

Impacto dos agentes antineoplásicos sobre os folículos ovarianos e importância das biotécnicas reprodutivas na preservação da fertilidade humana

The preservation of fertility in young women of reproductive age has become a major challenge in medicine, since most cancer treatments can cause premature ovarian failure due to ovarian toxicity of chemotherapeutic agents. Based on this sensitivity it is necessary to revert or minimize damage to reproductive cells resulting from chemotherapy. It have become more frequent studies and researches for alternatives to preserve female fertility, and treatments that are more selective for cancer cells. Currently there are several options for preservation of fertility in women undergoing chemotherapy treatments.This article aims to present an overview of the damage caused by chemotherapy ovarian function and possible options for preserving fertility in female cancer patients and prospects in oncofertilidade. A search on databases were searched for relevant articles: the National Library of Medicine (PubMed) and the Virtual Health Library. Articles published between 1967 and 2015 on chemotherapeutic agents and their damage on female fertility was held.

SAFETY AND TOLERABILITY OF ANTIEPILEPTIC DRUGS AT WOMEN WITH EPILEPSY (DATA OF SVT. LUKA’S INSTITUTE OF CHILD NEUROLOGY AND EPILEPSY)

Women with epilepsy are referred to the special risk group due to the development of side effects of antiepileptic drugs (АED). Women’s neuroendocrinal disorders can be caused by the disease itself-epilepsy, as well as by the undertaken therapy. We have carried out a retrospective research in order to assess the safety and the tolerance of different AED at young girls and women of reproductive age. Was analyzed the data base of patients of Svt. Luka’s Institute of Child Neurology and Epilepsy, comprising all patients, who have been monitored in the period between 2000 and 2014 inclusive at the age between 15–40 years (n = 301). The research included patients, with different diagnosed forms of focal or generalized epilepsy, who were taking AED both during mono and polytherapy. Were analyzed all cases of neuroendocrinal, especially reproductive disorders, including the considerable gain of weight, menstrual disorder, sterility at AED background. Also was analyzed the result of all registered pregnancies at women with epilepsy (at the background of the antiepileptic therapy, as well as without treatment during pregnancy). The retrospective data analysis has revealed 51 сase (17 % in the group under review) of expressed neuroendocrinal, reproductive and cosmetic side effects (including the menstrual disorder: dysmenorrhea, opsomenorrhea, amenorrhea, anovulatory cycles, sterility, unfavorable pregnancy outcomes, as well as cosmetic endocrinal side effects: obesity, hirsutism, hair loss. Most patients have got such combined side effects. Our research results show, that in most cases the pregnancy at women with epilepsy ends by birth of a healthy child, the pregnancy outcome depends on many factors, it also differs according to applied AED. Valproic acid drugs show the highest teratogenic risk. Also at the back ground of the therapy with valproic acid have been registered most cases of neuroendocrinal reproductive diseases at women, who had been included in our research. The second most frequent type of the teratogenic effect and reproductive diseases are AED of carbamazepine group. Most favorable results are shown, when new AED are applied (topiramate, levetiracetam, oxcarbazepine).

An estrogen-induced endometrial hyperplasia mouse model recapitulating human disease progression and genetic aberrations.

Endometrial hyperplasia (EH) is a condition originating from uterine endometrial glands undergoing disordered proliferation including the risk to progress to endometrial adenocarcinoma. In recent years, a steady increase in EH cases among younger women of reproductive age accentuates the demand of therapeutic alternatives, which emphasizes that an improved disease model for therapeutic agents evaluation is concurrently desired. Here, a new hormone-induced EH mouse model was developed using a subcutaneous estradiol (E2)-sustained releasing pellet, which elevates the serum E2 level in mice, closely mimicking the effect known as estrogen dominance with underlying, pathological E2 levels in patients. The onset and progression of EH generated within this model recapitulate a clinically relevant, pathological transformation, beginning with disordered proliferation developing to simple EH, advancing to atypical EH, and then progressing to precancerous stages, all following a chronologic manner. Although a general increase in nuclear progesterone receptor (PR) expression occurred after E2 expression, a total loss in PR was noted in some endometrial glands as disease advanced to simple EH. Furthermore, estrogen receptor (ER) expression in the nucleus of endometrial cells was reduced in disordered proliferation and increased when EH progressed to atypical EH and precancerous stages. This EH model also resembles other pathological patterns found in human disease such as leukocytic infiltration, genetic aberrations in β-catenin, and joint phosphatase and tensin homolog/paired box gene 2 (PTEN/PAX2) silencing. In summary, this new and comprehensively characterized EH model is cost-effective, easily reproducible, and may serve as a tool for preclinical testing of therapeutic agents and facilitate further investigation of EH.

Beneficial effects of co-treatment with dextromethorphan on prenatally methadone-exposed offspring.

BackgroundHeroin use among young women of reproductive age has drawn much attention around the world. Although methadone is widely used in maintenance therapy for heroin/morphine addiction, the long-term effects of prenatal exposure to methadone and preventative therapy remain unclear. For revealing this question, female pregnant Sprague–Dawley rats were sub-grouped to receive (1) vehicle, (2) methadone 5 mg/kg at embryonic day 3 (E3) and then 7 mg/kg from E4 to E20, (3) dextromethorphan (DM) 3 mg/kg, and (4) methadone + DM (the rats received methadone followed by DM treatment), subcutaneously, twice a day from E3 to E20. The body weight, natural withdrawal, pain sensitivity, ED50, conditioned place preference and water maze were conducted at different postnatal stages (P1 to P79) of offspring. The quantitative real-time RT-PCR and electrophysiology were also used to measure the gene expression of opioid receptors in the spinal cord and changes of LTP/LTD in the hippocampus, separately.ResultsPrenatal exposure to methadone or DM did not affect survival rate, body weight, water maze and LTP or LTD of offspring. However, prenatal methadone significantly increased the withdrawal symptoms, pain sensitivity, addiction liability and decreased the mRNA expression of pain related opioid receptors. Co-administration of DM with methadone in the maternal rats effectively prevented these abnormalities of offspring induced by methadone.ConclusionsOur study clearly showed that co-administration of dextromethorphan with methadone in the maternal rats prevented the adverse effects induced by prenatal methadone exposure. It implies that dextromethorphan may have a potential to be used in combination with methadone for maintenance treatment in pregnant heroin-addicted women to prevent the adverse effects induced by methadone on offspring.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-015-0126-2) contains supplementary material, which is available to authorized users.