Women with obesity and infertility are counseled to lose weight prior to conception and infertility treatment to improve pregnancy rates and birth outcomes, although confirmatory evidence from ...randomized trials is lacking. We assessed whether a preconception intensive lifestyle intervention with acute weight loss is superior to a weight neutral intervention at achieving a healthy live birth.
In this open-label, randomized controlled study (FIT-PLESE), 379 women with obesity (BMI ≥ 30 kg/m2) and unexplained infertility were randomly assigned in a 1:1 ratio to 2 preconception lifestyle modification groups lasting 16 weeks, between July 2015 and July 2018 (final follow-up September 2019) followed by infertility therapy. The primary outcome was the healthy live birth (term infant of normal weight without major anomalies) incidence. This was conducted at 9 academic health centers across the United States. The intensive group underwent increased physical activity and weight loss (target 7%) through meal replacements and medication (Orlistat) compared to a standard group with increased physical activity alone without weight loss. This was followed by standardized empiric infertility treatment consisting of 3 cycles of ovarian stimulation/intrauterine insemination. Outcomes of any resulting pregnancy were tracked. Among 191 women randomized to standard lifestyle group, 40 dropped out of the study before conception; among 188 women randomized to intensive lifestyle group, 31 dropped out of the study before conception. All the randomized women were included in the intent-to-treat analysis for primary outcome of a healthy live birth. There were no significant differences in the incidence of healthy live births standard 29/191(15.2%), intensive 23/188(12.2%), rate ratio 0.81 (0.48 to 1.34), P = 0.40. Intensive had significant weight loss compared to standard (-6.6 ± 5.4% versus -0.3 ± 3.2%, P < 0.001). There were improvements in metabolic health, including a marked decrease in incidence of the metabolic syndrome (baseline to 16 weeks: standard: 53.6% to 49.4%, intensive 52.8% to 32.2%, P = 0.003). Gastrointestinal side effects were significantly more common in intensive. There was a higher, but nonsignificant, first trimester pregnancy loss in the intensive group (33.3% versus 23.7% in standard, 95% rate ratio 1.40, 95% confidence interval CI: 0.79 to 2.50). The main limitations of the study are the limited power of the study to detect rare complications and the design difficulty in finding an adequate time matched control intervention, as the standard exercise intervention may have potentially been helpful or harmful.
A preconception intensive lifestyle intervention for weight loss did not improve fertility or birth outcomes compared to an exercise intervention without targeted weight loss. Improvement in metabolic health may not translate into improved female fecundity.
ClinicalTrials.gov NCT02432209.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Vitamin D has been linked to antimüllerian hormone levels, suggesting a possible association with greater ovarian reserve, but large population-based studies are lacking. Our objective was to explore ...the association between vitamin D and follicle-stimulating hormone (FSH) in premenopausal women.
The Uterine Fibroid Study (1996-1999) enrolled randomly selected 30- to 49-year-old members of a Washington, DC, health plan (N = 1,430). Women provided blood and urine samples in addition to questionnaire data. The vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) was measured in stored plasma samples. Urinary FSH (mIU/mg creatinine) was measured by immunofluorometric assay. To obtain baseline measures, we limited this investigation to urine samples collected in the first 5 days of the menstrual cycle or 5 days before menses onset. In addition, postmenopausal women and women using oral contraceptives were excluded, leaving 527 women for analysis. FSH was creatinine-adjusted, normalized by log transformation, and modeled with multivariable linear regression.
The median 25(OH)D level was 12 ng/mL, with approximately 75% of participants below the recommended level of 20 ng/mL. FSH and 25(OH)D were inversely related. For every 10-ng/mL increase in 25(OH)D, urinary FSH decreased by 14% (95% CI, -23 to -5; P = 0.003).
Vitamin D is inversely related to FSH. This is consistent with literature relating low vitamin D levels to lower antimüllerian hormone levels. Prospective studies should investigate whether low vitamin D levels contribute to decreased ovarian reserve.
To determine whether antioxidants improve male fertility, as measured by semen parameters and DNA fragmentation at 3 months and pregnancy resulting in live birth after up to 6 months of treatment, ...among couples with male factor infertility.
Multicenter, double-blind, randomized, placebo-controlled trial with an internal pilot study.
Nine fertility centers in the United States from December 2015 to December 2018.
Men (N = 174) with sperm concentration ≤15 million/mL, motility ≤40%, normal morphology ≤4%, or DNA fragmentation >25%, and female partners who were ovulatory, ≤40 years old, and had documented tubal patency.
Males randomly assigned to receive an antioxidant formulation (n = 85) containing 500 mg of vitamin C, 400 mg of vitamin E, 0.20 mg of selenium, 1,000 mg of l-carnitine, 20 mg of zinc, 1,000 μg of folic acid, 10 mg of lycopene daily, or placebo (n = 86). Treatment lasted for a minimum of 3 months and maximum of 6 months, and couples attempted to conceive naturally during the first 3 months and with clomiphene citrate with intrauterine insemination of the female partner in months 4 through 6.
Primary outcome was live birth; secondary outcomes included pregnancy within 6 months of treatment. For the internal pilot, the primary outcomes were semen parameters and sperm DNA fragmentation index after 3 months of treatment.
In the Males, Antioxidants, and Infertility (MOXI) study, after 3 months of treatment, the change in sperm concentration differed between the antioxidant group (median −4.0 interquartile range−12.0, 5.7 million/mL) and placebo group (+2.4 −9.0, 15.5 million/mL). However, there were no statistically significant differences between the two groups for changes in sperm morphology, motility, or DNA fragmentation. Among the 66 oligospermic men at randomization, sperm concentration did not differ at 3 months between the antioxidant and control groups: 8.5 (4.8, 15.0) million/mL versus 15.0 (6.0, 24.0) million/mL. Of the 75 asthenospermic men, motility did not differ at 3 months: 34% ± 16.3% versus 36.4% ± 15.8%. Among the 44 men with high DNA fragmentation, DNA fragmentation did not differ at 3 months: 29.5% (21.6%, 36.5%) versus 28.0% (20.6%, 36.4%). In the entire cohort, cumulative live birth did not differ at 6 months between the antioxidant and placebo groups: 15% versus 24%.
Antioxidants do not improve semen parameters or DNA integrity among men with male factor infertility. Although limited by sample size, this study suggests that antioxidant treatment of the male partner does not improve in vivo pregnancy or live-birth rates.
NCT02421887
El efecto de los antioxidantes en el factor masculino de infertilidad: ensayo clínico aleatorizado de hombres, antioxidantes e Infertilidad
Determinar si los antioxidantes mejoran la fertilidad masculina, según lo medido por los parámetros de semen y fragmentación del ADN a los 3 meses, y embarazo resultante en un nacido vivo después de 6 meses de tratamiento en parejas con infertilidad por factor masculino.
Ensayo multicéntrico, doble ciego, aleatorizado, controlado con placebo con un estudio piloto interno.
Nueve centros de fertilidad en los Estados Unidos desde diciembre del 2005 hasta diciembre del 2018.
Hombres (n= 174) con concentración de esperma ≤ 15 millones/ml, movilidad ≤ 4%, morfología normal ≤ 4%, o fragmentación del ADN > 25% y parejas femeninas las cuales eran ovulatorias, ≤ 40 años y tenían permeabilidad tubárica documentada.
Hombres asignados al azar para recibir una formulación antioxidante (n = 85) que contiene 500 mg de vitamina C, 400 mg de vitamina E, 0.20 mg de selenio, 1.000 mg de L-carnitina, 20mg de zinc, 1.000 ug de ácido fólico, 10 mg de licopeno diario o placebo (n= 86). El tratamiento duró un mínimo de 3 meses y un máximo de 6 meses y las parejas intentaron concebir naturalmente durante los primeros 3 meses y con citrato de clomifeno con inseminación intrauterina de la pareja femenina en los meses 4 a 6.
El primer resultado fue el nacimiento vivo, los segundos resultados incluyeron embarazo dentro de los 6 meses de tratamiento. Para el piloto interno, el primer resultado fueron los parámetros de semen e índice de fragmentación del ADN espermático después de 3 meses de tratamiento.
En el estudio Masculinos, Antioxidantes e Infertilidad (MOXI), después de 3 meses de tratamiento, el cambio en la concentración de esperma difirió entre el grupo antioxidante (mediana -4,0 rango intercuartil -12.0- 5,7 millones / mL) y el grupo placebo (+2,4 9,0- 15,5 millones / ml). Sin embargo, no hubo diferencias estadísticamente significativas entre los dos grupos para los cambios de morfología, motilidad o fragmentación del ADN espermático. Entre los 66 hombres oligospérmicos aleatorizados, la concentración de esperma no difirió a los 3 meses entre los grupos antioxidante y control: 8,5 (4,8- 15,0) millones / ml versus 15,0 (6,0- 24,0) millones / ml. De los 75 hombres astenospérmicos, la motilidad no difirió a los 3 meses: 34% ± 16,3% versus 36,4% ± 15,8%. Entre los 44 hombres con alta fragmentación del ADN, la fragmentación del ADN no difirió a los 3 meses: 29,5% (21,6% - 36,5%) versus 28,0% (20,6% - 36,4%). En toda la cohorte, la tasa acumulada de nacido vivo no difirió a los 6 meses entre los grupos de antioxidantes y placebo: 15% versus 24%.
Los antioxidantes no mejoran los parámetros de semen o integridad del ADN entre los hombres con infertilidad por factor masculino. Aunque limitado por el tamaño muestral, este estudio sugiere que el tratamiento de la pareja masculina con antioxidantes no mejora las tasas de embarazo o nacido vivo.
Objective To evaluate the impact of a short luteal phase on fecundity. Design Prospective time-to-pregnancy cohort study. Setting Not applicable. Patient(s) Women trying to conceive, ages ...30–44 years, without known infertility. Intervention(s) Daily diaries, ovulation prediction testing, standardized pregnancy testing. Main Outcome Measure(s) Subsequent cycle fecundity. Result(s) Included in the analysis were 1,635 cycles from 284 women. A short luteal phase (≤11 days including the day of ovulation) occurred in 18% of observed cycles. Mean luteal phase length was 14 days. Significantly more women with a short luteal phase were smokers. After adjustment for age, women with a short luteal phase had 0.82 times the odds of pregnancy in the subsequent cycle immediately following the short luteal phase compared with women without a short luteal phase. Women with a short luteal length in the first observed cycle had significantly lower fertility after the first 6 months of pregnancy attempt, but at 12 months there was no significant difference in cumulative probability of pregnancy. Conclusion(s) Although an isolated cycle with a short luteal phase may negatively affect short-term fertility, incidence of infertility at 12 months was not significantly higher among these women. Clinical Trial Registration Number NCT01028365.
•PFC levels in our cohort were consistent with levels seen in the general US population of reproductive age women.•There was positive correlation between PFCs measured in this study.•Although PFC ...levels were correlated with thyroid hormone levels, there was not a strong nor a significant association with ovarian reserve.•In our cohort, fecundability was not associated with serum PFC levels.
Perfluorinated chemicals (PFCs) can act as endocrine-disrupting chemicals, but there has been limited study of their effects on ovarian reserve or fecundability. 99 women, 30–44 years old, without infertility were followed until pregnancy. Initially, serum was evaluated for Antimullerian hormone (AMH), thyroid hormones: thyroid stimulating hormone (TSH), thyroxine (T4), free thyroxine (fT4), and triiodothyronine (T3), and PFCs: perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS). Bivariate analyses assessed the relationship between thyroid hormones, AMH, and PFCs. Fecundability ratios (FR) were determined for each PFC using a discrete time-varying Cox model and a day-specific probability model. PFC levels were positively correlated with each other (r 0.24–0.90), but there was no correlation with TSH (r 0.02–0.15) or AMH (r −0.01 to −0.15). FR point estimates for each PFC were neither strong nor statistically significant. Although increased exposure to PFCs correlates with thyroid hormone levels, there is no significant association with fecundability or ovarian reserve.
Local inflammation plays an important role in normal folliculogenesis and ovulation, and conditions of chronic systemic inflammation, such as obesity and polycystic ovarian syndrome, can disrupt ...normal follicular dynamics.
This study aimed to determine the association between systemic inflammation, as measured by C-reactive protein levels, and menstrual cycle length.
This study was a secondary analysis using data from Time to Conceive, a prospective time-to-pregnancy cohort study. The association between cycle length and C-reactive protein was analyzed using multivariable linear mixed and marginal models adjusted for age, race, education, body mass index, time since oral contraceptive use, alcohol, smoking, caffeine consumption, and exercise. Time to Conceive enrolled women aged 30 to 44 years with no history of infertility who were attempting to conceive for <3 months. Serum C-reactive protein levels were measured on cycle day 2, 3, or 4. Participants recorded daily menstrual cycle data for ≤4 months.
Main outcome measures included menstrual cycle length and follicular and luteal phase lengths. Multivariable analysis included 1409 cycles from 414 women. There was no linear association between C-reactive protein levels and menstrual cycle length. However, compared with <1 mg/L, a C-reactive protein level >10 mg/L was associated with >3 times the odds (adjusted odds ratio, 3.7; 95% confidence interval, 1.67–8.11) of long cycles (defined as ≥35 days). When evaluating follicular phase length, a C-reactive protein level of >10 mg/L was associated both with follicular phases that were 1.7 (95% confidence interval, 0.23–3.09) days longer and with >2 times the odds of a long follicular phase (adjusted odds ratio, 2.2; 95% confidence interval, 1.05–4.74).
There is a potential pathophysiological association between systemic inflammation and menstrual cycle changes. Further studies are needed to determine if systemic inflammation alters the menstrual cycle or if long menstrual cycles are a marker for elevated systemic inflammation.
Abstract Background The study was conducted to examine the impact of oral contraceptives (OCs) on serum antimullerian hormone (AMH) levels by obesity status in reproductive-age women. Study Design ...Ovulatory women, ages 18–35 years, of normal (<25 kg/m2 ; n =10) and obese (>30 kg/m2 ; n =10) body mass index (BMI) received a low-dose OC (20 mcg ethinyl estradiol/100 mcg levonorgestrel) for two cycles. Serum samples obtained at several time points during active pill use and hormone-free intervals were analyzed for AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and inhibin B. Results AMH levels did not differ by OC cycle day in either BMI group. On average, AMH levels were 34% lower in the obese group (2.9±2.1 vs. 4.4±1.8 ng/mL, p<.05). Modeling to determine differences in AMH throughout the cycle based on obesity status demonstrated significantly lower levels (p<.05), whereas serum AMH, FSH, LH, estradiol and inhibin B levels revealed no correlations when all time points were included. Conclusions In reproductive-age women, serum AMH levels do not appear to fluctuate during OC use, but AMH levels are significantly lower in obese women. Lower levels do not appear to be due to differences in gonadotropin levels or ovarian activity.
The effect of antidepressants on fertility Casilla-Lennon, Marianne M., BS; Meltzer-Brody, Samantha, MD; Steiner, Anne Z., MD, MPH
American journal of obstetrics and gynecology,
09/2016, Letnik:
215, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Background Information on the effects of different pharmaceuticals on fertility is sparse. Human and animal models indicate that antidepressant use could have a negative effect on fertility through ...alteration of levels of the neurosteroid, allopregnanolone. Objective The objective of this study is to assess the effects of antidepressants on the natural fertility in women. Study Design A secondary analysis of data from Time to Conceive, a prospective cohort study, was conducted. Women ages 30 to 44 years without a history of infertility, early in their attempts to conceive, were followed with standardized pregnancy testing until pregnancy was detected. Medication use was assessed at enrollment, daily for up to 4 months, and then monthly. For this analysis, discrete time regression models were created to calculate the association between antidepressant use and fecundability. Potential confounders—age, body mass index, caffeine, alcohol use, and education—were included in all models. Results Ninety-two (9.6%) of 957 women reported antidepressant use while attempting to conceive. Women taking antidepressants were more likely to be non-Hispanic Caucasian (91% vs 75%, P < .01) and to consume alcoholic beverages (74% vs 61%, P < .01). Antidepressant use at enrollment had an adjusted fecundability ratio (FR) of 0.86 (95% confidence interval CI, 0.63–1.20). However, time-varying analyses suggested that antidepressant use in a given cycle is associated with a reduced probability of conceiving in that cycle (adjusted FR, 0.75; 95% CI, 0.53–1.06). After adjusting for history of depression or restricting the analysis to women who reported a history of depression, the association between antidepressant use and decreased fecundability remained adjusted FR, 0.66 (95% CI, 0.45–0.97) and (adjusted FR, 0.64; 95% CI, 0.43–0.94), respectively. Conclusion Our data suggest that antidepressants may reduce the probability of a woman with a history of depression to conceive naturally. Future studies are needed to differentiate the extent to which this association is due to the antidepressant itself versus the underlying depression.
In animals, low levels of vitamin D are associated with estrus cycle disturbances, but there are virtually no human data. We examined the association of 25-hydroxyvitamin D (25(OH)D) (a biomarker for ...vitamin D status) with menstrual cycle characteristics.
Women aged 35-44 were randomly selected from a Washington D.C. health plan and invited to participate in the Uterine Fibroid Study (1996-1999). Our analysis includes 636 women (57% were African-American) who provided a blood sample and completed a telephone interview that included gynecologic history. Women were asked their usual cycle length in the preceding year. Women who reported it was "too irregular to estimate" were classified as having irregular cycles (N=48). Women were excluded if they currently or recently used hormonal contraception or any other medication that influences menstrual cycles. 25(OH)D was measured by radioimmunoassay in stored plasma samples.
The median 25(OH)D level was 12.0 ng/mL (interquartile range: 7.6, 19.7 ng/mL). After controlling for age, race, BMI, education, age of menarche, current smoking, alcohol use, and physical activity, a decrease in 25(OH)D of 10 ng/mL was associated with 1.9 times the odds of irregular cycles (Odds ratio (OR) (95% confidence interval (CI)): 1.9 (1.0, 3.4), p=0.04). 25(OH)D was not associated with the occurrence of short cycles (OR(CI): 1.08 (0.79, 1.48, p=0.6) or long cycles (OR(CI): 1.31 (0.66, 2.60), p=0.4).
Lower levels of 25(OH)D were associated with irregular cycles, but not with short or long cycles. Vitamin D may play a role in regulating ovulatory function. Further investigation of potential mechanisms is warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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