Marlene B. Goldman

Oxidative stress and antioxidants: exposure and impact on female fertility

BACKGROUNDnReproductive failure is a significant public health concern. Although relatively little is known about factors affecting fertility and early pregnancy loss, a growing body of literature suggests that environmental and lifestyle factors play an important role. There is sufficient evidence to hypothesize that diet, particularly its constituent antioxidants, and oxidative stress (OS) may influence the timing and maintenance of a viable pregnancy. We hypothesize that conditions leading to OS in the female affect time-to-pregnancy and early pregnancy loss.nnnMETHODSnWe review the epidemiology of female infertility related to antioxidant defenses and oxidation and examine potential sources of OS from the ovarian germ cell through the stages of human pregnancy and pregnancy complications related to infertility. Articles were identified through a search of the PubMed database.nnnRESULTSnFemale OS is a likely mediator of conception and threshold levels for OS exist, dependent on anatomic location and stage of preconception.nnnCONCLUSIONSnProspective pregnancy studies with dietary assessment and collection of biological samples prior to conception with endpoints of time-to-pregnancy and early pregnancy loss are needed.

A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial

OBJECTIVEnTo determine the value of gonadotropin/intrauterine insemination (FSH/IUI) therapy for infertile women aged 21-39 years.nnnDESIGNnRandomized controlled trial.nnnSETTINGnAcademic medical center associated with a private infertility center.nnnPATIENT(S)nCouples with unexplained infertility.nnnINTERVENTION(S)nCouples were randomized to receive either conventional treatment (n=247) with three cycles of clomiphene citrate (CC)/IUI, three cycles of FSH/IUI, and up to six cycles of IVF or an accelerated treatment (n=256) that omitted the three cycles of FSH/IUI.nnnMAIN OUTCOME MEASURE(S)nThe time it took to establish a pregnancy that led to a live birth and cost-effectiveness, defined as the ratio of the sum of all health insurance charges between randomization and delivery divided by the number of couples delivering at least one live-born baby.nnnRESULT(S)nAn increased rate of pregnancy was observed in the accelerated arm (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.00-1.56) compared with the conventional arm. Median time to pregnancy was 8 and 11 months in the accelerated and conventional arms, respectively. Per cycle pregnancy rates for CC/IUI, FSH/IUI, and IVF were 7.6%, 9.8%, and 30.7%, respectively. Average charges per delivery were

Impact of oxidative stress on female fertility.

9,800 lower (95% CI,

Preconception folate and vitamin B6 status and clinical spontaneous abortion in Chinese women

25,100 lower to

A randomized clinical trial to determine optimal infertility treatment in older couples: the Forty and Over Treatment Trial (FORT-T)

3,900 higher) in the accelerated arm compared to conventional treatment. The observed incremental difference was a savings of

Female dietary antioxidant intake and time to pregnancy among couples treated for unexplained infertility.

2,624 per couple for accelerated treatment and 0.06 more deliveries.nnnCONCLUSION(S)nA randomized clinical trial demonstrated that FSH/IUI treatment was of no added value.

Optimizing the number of cleavage stage embryos to transfer on day 3 in women 38 years of age and older : a Society for Assisted Reproductive Technology database study

Purpose of review To review the role of oxidative stress in the context of female fertility. Recent findings Oxidative stress is associated with decreased female fertility in animal and in-vitro models, but no studies to date have directly assessed the relationship in women. Exposures associated with oxidative stress and with evidence to influence the timing and maintenance of a viable pregnancy include pregnancy complications (e.g. preeclampsia), extremes of body weight, alcohol, tobacco, and caffeine intake. Intake of antioxidant nutrients, including use of multivitamins, impacts the generation of reactive oxygen species and may play a beneficial role in female fertility. Summary Infertility is a significant public health problem and diagnosis and treatment are stressful, invasive, and costly. The role of oxidative stress in female fertility is an understudied and compelling area for investigation. Identifying modifiable factors to decrease oxidative stress in the gynecologic environment may be an inexpensive and noninvasive therapy for increasing fertility.

Gonadotropin therapy: a 20th century relic

OBJECTIVE To assess the association between preconception homocysteine and B vitamin status and risk of clinical spontaneous abortion in women from Anqing, China. METHODS All women were aged 21–34 years, had never smoked, and were primigravid. Patients (n = 49) were women with a clinically recognized pregnancy who experienced a fetal death before 100 days gestation. Controls (n = 409) were women who maintained a pregnancy that ended in a live birth. Homocysteine, folate, and vitamins B6 and B12 concentrations were measured in plasma obtained before conception. RESULTS Mean vitamin B6 concentration was lower in patients than in controls (34.0 versus 37.9 nmol/L, P = .04). In addition, the risk of spontaneous abortion tended to increase with decreasing plasma vitamin B6 and folate concentration (P for trend = .06 and .07, respectively), although the significance of these trends was further reduced in logistic models that included age, body mass index, and both vitamins. The risk of spontaneous abortion was four‐fold higher among women with suboptimal plasma concentrations of both folate and vitamin B6 (folate less than or equal to 8.4 nmol/L and vitamin B6 less than or equal to 49 nmol/L) than in those with higher plasma concentrations of both vitamins (odds ratio 4.1, 95% confidence interval 1.2, 14.4). Homocysteine and vitamin B12 status were not associated with spontaneous abortion risk. CONCLUSION Suboptimal preconception folate and vitamin B6 status, especially when they occur together, may increase the risk of clinical spontaneous abortion. Additional prospective studies are needed to confirm these findings and to determine whether antenatal B vitamin supplementation reduces spontaneous abortion risk.

When is clomiphene or gonadotropin intrauterine insemination futile? Results of the Fast Track and Standard Treatment Trial and the Forty and Over Treatment Trial, two prospective randomized controlled trials

OBJECTIVEnTo determine the optimal infertility therapy for women at the end of their reproductive potential.nnnDESIGNnRandomized clinical trial.nnnSETTINGnAcademic medical centers and private infertility center in a state with mandated insurance coverage.nnnPATIENT(S)nCouples with ≥ 6 months of unexplained infertility; female partner aged 38-42 years.nnnINTERVENTION(S)nRandomized to treatment with two cycles of clomiphene citrate (CC) and intrauterine insemination (IUI), follicle stimulating hormone (FSH)/IUI, or immediate IVF, followed by IVF if not pregnant.nnnMAIN OUTCOME MEASURE(S)nProportion with a clinically recognized pregnancy, number of treatment cycles, and time to conception after two treatment cycles and at the end of treatment.nnnRESULT(S)nWe randomized 154 couples to receive CC/IUI (N = 51), FSH/IUI (N = 52), or immediate IVF (N = 51); 140 (90.9%) couples initiated treatment. The cumulative clinical pregnancy rates per couple after the first two cycles of CC/IUI, FSH/IUI, or immediate IVF were 21.6%, 17.3%, and 49.0%, respectively. After all treatments, 110 (71.4%) of 154 couples had conceived a clinically recognized pregnancy, and 46.1% had delivered at least one live-born baby; 84.2% of all live-born infants resulting from treatment were achieved via IVF. There were 36% fewer treatment cycles in the IVF arm compared with either COH/IUI arm, and the couples conceived a pregnancy leading to a live birth after fewer treatment cycles.nnnCONCLUSION(S)nA randomized controlled trial in older women with unexplained infertility to compare treatment initiated with two cycles of controlled ovarian hyperstimulation/IUI versus immediate IVF demonstrated superior pregnancy rates with fewer treatment cycles in the immediate IVF group.nnnCLINICAL TRIAL REGISTRATION NUMBERnNCT00246506.

A randomized controlled trial comparing two types of retractors at caesarean delivery

OBJECTIVEnTo determine whether increased antioxidant intake in women is associated with shorter time to pregnancy (TTP) among a cohort of couples being treated for unexplained infertility.nnnDESIGNnSecondary data analysis of a randomized controlled trial.nnnSETTINGnAcademic medical center associated with a private infertility center.nnnPATIENTSnFemales with unexplained infertility.nnnINTERVENTIONSnNone.nnnMAIN OUTCOME MEASURE(S)nThe time it took to establish a pregnancy that led to a live birth.nnnRESULT(S)nMean nutrient intake exceeded the estimated average requirement (EAR) for vitamins C and E. No differences in mean intake of any of the antioxidants were noted between women who delivered a live-born infant during the study period vs. those who did not. In multivariable models, intake of β-carotene from dietary supplements was associated with shorter TTP among women with body mass index (BMI) ≥25 kg/m(2) (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.09-1.53) and women <35 y (HR 1.19, 95% CI 1.01-1.41). Intake of vitamin C from dietary supplements was associated with shorter TTP among women with BMI <25 kg/m(2) (HR 1.09, 95% CI 1.03-1.15) and women <35 y (HR 1.10, 95% CI 1.02-1.18). Intake of vitamin E from dietary supplements among women ≥35 y also was associated with shorter TTP (HR 1.07, 95% CI 1.01-1.13).nnnCONCLUSION(S)nShorter TTP was observed among women with BMI <25 kg/m(2) with increasing vitamin C, women with BMI ≥25 kg/m(2) with increasing β-carotene, women <35 y with increasing β-carotene and vitamin C, and women ≥35 y with increasing vitamin E.nnnCLINICAL TRIAL REGISTRATION NUMBERnNCT00260091.