Oral sildenafil citrate: a potential approach for improvement of endometrial thickness and treatment of unexplained infertility in women.

OBJECTIVE: The study aimed to determine the impact of using sildenafil citrate as an adjuvant with clomiphene citrate (CC) in the treatment of women with unexplained infertility. PATIENTS AND METHODS: 130 women with unexplained infertility were enrolled in a prospective randomized study. After dividing into two groups, all patients received CC 50 mg-BD from the 2nd to the 7th day of the cycle. Oral sildenafil citrate 20 mg was given BD to the study group from the end of menstruation till ovulation. A transvaginal ultrasound was carried out for all patients to assess ovulation, number of follicles, and endometrial thickness (ET). The beta-hCG blood test was used to determine pregnancy two weeks after ovulation followed by an ultrasound to confirm viability. Adverse effects were recorded and miscarriage, ectopic, and multi-fetal pregnancy were followed up for twelve weeks. RESULTS: Median ET in the study group was 8 mm compared to 7 mm in the control group (p<0.01). The number of pregnancies increased in the study group but with no significant difference. The median ET was greater in the study group with an infertility duration of less than 2 years. Headache was the most significant adverse effect in the study group (9.2% vs. 1.5%, p=0.052). CONCLUSIONS: Adding sildenafil citrate to CC is a good choice for overcoming the antiestrogenic action of CC and improving ET in women with unexplained infertility, especially in those with less than 2 years of infertility.

Ondansetron pharmacokinetics in pregnant women and neonates: towards a new treatment for neonatal abstinence syndrome.

Ondansetron is the drug of choice to prevent nausea in women undergoing cesarean surgery and can be used to prevent neonatal abstinence syndrome (NAS). The pharmacokinetics of ondansetron have not been characterized in pregnant women or in newborns. A nonlinear mixed-effects modeling approach was used to analyze plasma samples obtained from 20 nonpregnant and 40 pregnant women following a single administration of 4 or 8 mg ondansetron, from umbilical cord blood at delivery, and from neonates after birth. The analysis indicates that: ondansetron disposition is not affected by pregnancy (P > 0.05), but influenced by dose (P < 0.05), and is characterized by rapid transplacental transfer and longer elimination half-life in neonates compared to their mother. A dosing regimen for prevention of NAS was designed based on the model. The regimen involves IV administration of 4 mg to the mothers shortly before cord clamping, or oral administration of 0.07 mg/kg (or equivalently 0.04 mg/kg IV) to neonates.