Effects of Alpha-Lipoic Acid and Myoinositol Supplementation on the Oocyte Enviroment of Obese Infertile Women

INTRODUCTION Obesity is characterized by increased inflammation and oxidative stress, resulting in adverse effects on women reproductive potential. Antioxidant supplementation may exert a positive effect on the obese ovarian environment. Indeed, we preliminarily observed a reduction of mitochondrial (mt) DNA content, a marker of oxidative stress, in granulosa cells of obese infertile women supplemented with Sinopol\uae (Laborest SpA), composed by alpha-lipoic acid (ALA) 800 mg, myoinositol (MYO) 2 g, folic acid (FA) 400 ug. This suggested a potential role of Sinopol\uae in reducing oxidative stress in the obese ovarian environment. Here we analyzed Total Antioxidant Capacity (TAC) in follicular fluid and mtDNA levels in granulosa cells, in a larger population of infertile women undergoing in vitro fertilization (IVF). METHODS 19 normal weight (NW) and 24 obese (OB) infertile women were enrolled in our IVF center. Infertility was investigated and a non-ovarian diagnosis was made. Patients did not present any additional pathology. All women were provided with FA and among them 15 OB (OB-SIN) were also supplemented with ALA and MYO, for 2 months before ovarian stimulation. Follicular fluid (FF) and granulosa cells (GC) were collected after oocyte retrieval. TAC was measured in FF by enzymatic assay, mtDNA levels evaluated in GC by Real-time PCR. Results were compared by ANOVA and correlations assessed by Pearson\u2019s correlation (SPSS; IBM). RESULTS OB groups had similar BMI (OB patients supplemented with only folic acid (OB-F): 30.2 \ub1 0.7; OB-SIN: 32.7 \ub1 1.1 kg/m2). Women age was similar in all groups (NW: 36.7 \ub1 0.6; OB-F: 37.6 \ub1 1.7; OB-SIN: 35.9 \ub1 1.1 years). Among OB women, antioxidant capacity was significantly higher in OB-SIN than in OB-F. mtDNA levels showed an opposite trend, being decreased in OB-SIN and increased in OB-F compared to NW, though not reaching statistical significance. mtDNA levels were significantly and inversely correlated with the number of total oocytes and metaphase II (mature) oocytes. Pregnancy rate was similar in NW (36.8%) and OB-SIN (33.3%) women, while it was lower in OB-F patients (11.1%). CONCLUSION We analyzed molecular markers in granulosa cells and follicular fluid as indicators of oocytes oxidative state. Our results suggest that supplementation with a compound of ALA -a natural antioxidant, cofactor in the mt respiratory chain- and MYO -an insulin-sensitizer- might increase antioxidant defenses and reduce oxidative stress in the obese ovarian environment, possibly contributing at restoring physiological conditions. This might improve IVF pregnancy rates in obese infertile women. Further studies are needed to clarify the synergic action of ALA, MYO and FA on the oocyte oxidative environment. Supported by Laborest Sp

Treatment of viral hepatitis in pregnancy

Viral hepatitis can be caused by the hepatitis A, B, C, D and E viruses. In the Western world, hepatitis A, B or C do not seem to influence the course of pregnancy, whereas hepatitis E infection, when contracted during the second or third trimester, seems to have a higher risk of developing into a fulminant hepatitis. Mother-to-infant transmission of hepatitis A seems to be very uncommon. The majority of HBsAg-positive and HBeAg-positive mothers can transmit the disease vertically. The timing of transmission is predominantly peripartum, and newborns of HBsAg-positive mothers should receive hepatitis B immunoglobulins within 12 h of birth, with HBV vaccine at birth and 1 and 6 months later. Hepatitis C is more often a chronic disease. Vertical transmission of hepatitis C is considered to be relatively rare but high viraemia or coinfection with HIV can increase this risk. There is currently no treatment to prevent this vertical transmission and pregnancies among HCV-positive mothers should not be discouraged. Infants should be tested for anti-HCV at 1 year and followed for the development of hepatitis. Breast feeding does not seem to play an important role in the transmission of hepatitis B and

Antiretroviral therapy during pregnancy

- Treatment with zidovudine has led to a fall in the mother-to-child HIV transmission during pregnancy and the first few weeks of neonatal life. - Ongoing trials are assessing the preventive efficacy of two-drug and three-drug antiretroviral regimens in this setting. - Pending the results of these studies, treatment with zidovudine is recommended for all HIV-infected pregnant women. - Current therapeutic strategies may lead to the prescription or continuation of multidrug antiretroviral regimens for seropositive pregnant women. - Available information on the possible adverse effects of antiretroviral drugs on the pregnant woman, fetus and child are limited. - Two reports propose similar guidelines for the management of seropositive pregnant women and their children during the first weeks of life

Reproductive assistance in HIV serodiscordant couples

BACKGROUND Three quarters of individuals infected with human immunodeficiency virus (HIV) are in their reproductive years and may consider pregnancy planning. Techniques have been developed which can minimize the risk of HIV transmission in these couples, and the current literature on this topic is reviewed here. METHODS We reviewed the literature for the following topics: risk of HIV transmission, effects of HIV infection on fertility, reproductive assistance in industrialized and low-income countries, pre-exposure chemoprophylaxis (PrEP) and timed intercourse in HIV-discordant couples for both male and female positivity. Relevant publications were identified through searches of the EMBASE Medline and PubMed databases, the Google-indexed scientific literature and periodic specialized magazines from the on-line Library Service of the University of Milan, Italy. RESULTS In serodiscordant couples in which the man is positive, the primary method used to prevent HIV transmission is 'sperm washing', followed by IUI or IVF. Data show that sperm washing in HIV-positive men has not produced seroconversion in women or their offspring; however, the evidence is limited. Recently, increasing evidence describing PrEP for HIV prevention has been published and PrEP could be an alternative to ART for fertile couples. Usually HIV-infected women undergo self-insemination around the time of ovulation. Few studies have been published on IVF outcome in HIV-infected women. CONCLUSIONS Assisted reproduction programmes should be integrated into global public health services against HIV. For HIV serodiscordant couples with infected men, sperm washing should be the first choice. However, timed intercourse and PrEP for HIV prevention has been reported. Recent data highlight the possible impairment of fertility in HIV-infected women. Efforts to design a multicentric study should be strengthened

Maternal estradiol and progesterone concentrations among singleton spontaneous pregnancies during the first trimester

Background: Pregnancy hormonal milieu represents a crucial determinant of fetal outcome. We aim to determine 17\u3b2-estradiol (E2) and progesterone (PGT) concentrations in spontaneous pregnancies during the first trimester. In addition, we aim to determine E2 concentrations as a function of gestational age (GA) and PGT. Methods: Between November 2015 and March 2017, 104 healthy women of at least 18\ua0years undergoing medical consultation for voluntary interruption of pregnancy were enrolled in an observational study at University Hospital ASST Fatebenefratelli Sacco, Milan, Italy. Only singleton pregnancies between 5+0 and 13+6 weeks of gestation were eligible. First trimester ultrasound scans were performed for dating and one fasting venous blood sample was collected for E2 and PGT determinations. Results: E2 and PGT concentrations steadily increased according to GA. The correlation between E2 on a logarithmic scale and PGT concentrations was expressed by the following equation, explaining 12.6% of E2 variance: logE2 = 2.57 + 0.1 7 PGT, (r = 0.34, p < 0.001). By performing a multivariable linear regression analysis adjusted for variables significantly correlated with E2 concentrations, we obtained a model explaining the 53.5% of E2 variance. The final equation to determine E2 concentrations among Caucasian women was: logE2 = 1.96 + 0.01 7 GA + 0.004 7 PGT. Conclusions: Gestational week-specific reference intervals are reported for maternal E2 and PGT concentrations during early pregnancy, further providing a model for E2 assessment in this period. This will represent a starting point for further evaluations between twin and ART pregnancies, as well as to potentially improve pregnancy outcome and future health of the offspring

Maternal and fetal outcomes in oocyte donation pregnancies

BACKGROUND: Since the first successful use of donated oocytes in 1984, the number of oocyte donation cycles in Europe and the USA has dramatically increased. Consequently, there has been increasing interest in the impact of oocyte donation on maternal and fetal outcomes. OBJECTIVE AND RATIONALE: The aim of this review was to summarize the literature regarding maternal and fetal outcomes from pregnancies conceived through oocyte donation. SEARCH METHODS: Identification of relevant publications was through research within the Embase Medline and PubMed databases, the Google-indexed scientific literature and periodic specialized magazines from the on-line Library Service of the University of Milan. OUTCOMES: Oocyte donation seems to be independently associated with a higher rate of pregnancy-induced hypertension and pre-eclampsia. An explanatory hypothesis is that an immunological maladaptation causes placenta-mediated disorders in oocyte donation pregnancies. The risks are even higher in twin pregnancies. Oocyte donation also seems to be associated with lower fetal birthweight. However, after adjusting for obstetric complications, most studies report less pronounced differences in birthweight or no dissimilarities. The incidence of cesarean section is increased without clear clinical indications. WIDER IMPLICATIONS: Oocyte donation pregnancies are associated with a higher rate of placental disorders of pregnancy, such as gestational hypertension and pre-eclampsia. The risk of poorer neonatal outcomes is increased in oocyte donation pregnancies compared to other in-vitro fertilization pregnancies. Poorer outcomes have been demonstrated especially for twin pregnancies and in association with previous chronic pathologies or the development of obstetrics complications

Micronutrient supplementation in pregnancy: Who, what and how much?

Pregnancy represents a period of major physiological and metabolic change, aiming to ensure proper fetal growth and development, as well as maternal preservation. This review focuses on maternal nutrition, and particularly on micronutrient deficiencies and supplementation during pregnancy. Nutrient deficiencies and consequences in pregnant women are presented, with an overview of current recommendations for dietary supplementation in pregnancy, even considering the risk of micronutrient overload. Appropriate universal supplementation and prophylaxis/treatment of nutritional needs currently appear to be the most cost-effective goal in low-income countries, thus ensuring adequate intake of key elements including folate, iron, calcium, vitamin D and A. In high-income countries, a proper nutritional assessment and counselling should be mandatory in obstetric care in order to normalize pregestational body mass index, choose a healthy dietary pattern and evaluate the risk of deficiencies