BackgroundWomen with hyper-and hypothyroidism are at increased risk for infertility and adverse pregnancy outcomes. Whether in women considered euthyroid thyroid function (TSH values) and thyroid autoimmunity (thyroid antibodies) influence in vitro fertilization (IVF) cycle outcome has, however, remained controversial. Any such effect should be easily visible in women with low functional ovarian reserve (LFOR) and thus small oocyte and embryo numbers.MethodsWe evaluated the relationship between TSH levels and embryo quality in euthyroid women with LFOR undergoing IVF. Mean age for the study population was 39.9 ± 4.6 years. Embryo quality was assessed in 431 embryos from 98 first IVF cycles according to TSH levels (with cut-off 2.5μIU/mL), and to presence versus absence of thyroid autoantibodies.ResultsMean Anti Mullerian hormone (AMH) was 0.8 ± 0.8 ng/mL and mean TSH was 1.8 ± 0.9 μIU/mL. Comparable embryo quality was observed in women with TSH ≤ and >2.5μIU/mL. TPO antibodies significantly affected embryo quality in women with low-normal TSH levels (P = 0.045). In women with high-normal TSH levels, increasing TSH had a negative impact on embryo quality (P = 0.027). A trend towards impaired embryo quality with TPO antibodies was also observed in these patients (p = 0.057).ConclusionsTPO antibodies affect embryo quality in euthyroid women with low-normal TSH ≤2.5 μIU/mL. In women with high-normal TSH levels, increasing TSH levels, and possibly TPO antibodies, appear to impair embryo quality. These results suggest that the negative impact of thyroid autoimmunity becomes apparent, once thyroid hormone function is optimized.
ContextMutations of the fragile X mental retardation 1 (FMR1) gene are associated with distinct ovarian aging patterns.ObjectiveTo confirm in human in vitro fertilization (IVF) that FMR1 affects outcomes, and to determine whether this reflects differences in ovarian aging between FMR1 mutations, egg/embryo quality or an effect on implantation.Design, Setting, PatientsIVF outcomes were investigated in a private infertility center in reference to patients' FMR1 mutations based on a normal range of CGGn = 26–34 and sub-genotypes high (CGGn>34) and low (CGG<26). The study included 3 distinct sections and study populations: (i) A generalized mixed-effects model of morphology (777 embryos, 168 IVF cycles, 125 infertile women at all ages) investigated whether embryo quality is associated with FMR1; (ii) 1041 embryos in 149 IVF cycles in presumed fertile women assessed whether the FMR1 gene is associated with aneuploidy; (iii) 352 infertile patients (< age 38; in 1st IVF cycles) and 179 donor-recipient cycles, assessed whether the FMR1 gene affects IVF pregnancy chances via oocyte/embryo quality or non-oocyte maternal factors.InterventionsStandardized IVF protocols.Main Outcome MeasuresMorphologic embryo quality, ploidy and pregnancy rates.Results(i) Embryo morphology was reduced in presence of a low FMR1 allele (P = 0.032). In absence of a low allele, the odds ratio (OR) of chance of good (vs. fair/poor) embryos was 1.637. (ii) FMR1 was not associated with aneuploidy, though aneuploidy increased with female age. (iii) Recipient pregnancy rates were neither associated with donor age or donor FMR1. In absence of a low FMR1 allele, OR of clinical pregnancy (vs. chemical or no pregnancy) was 2.244 in middle-aged infertility patients.ConclusionsA low FMR1 allele (CGG<26) is associated with significantly poorer morphologic embryo quality and pregnancy chance. As women age, low FMR1 alleles affect IVF pregnancy chances by reducing egg/embryo quality by mechanisms other than embryo aneuploidy.
We examined the association between midtrimester intra-amniotic sludge and spontaneous preterm birth (PTB) in asymptomatic women undergoing amniocentesis. We performed a prospective cohort study of women having an amniocentesis for fetal karyotyping between 14 and 24 weeks' gestation. Cervical length and the presence of amniotic sludge were assessed by transvaginal ultrasound. Amniotic fluid concentrations of matrix metalloproteinase-8, glucose and lactate were measured. Early (<32 weeks) and late (32 to 36 weeks) preterm premature rupture of membranes (PPROM) and spontaneous PTB constituted primary outcomes. Nonparametric analyses were conducted. Three hundred ten women, including 94 (30%) with free-floating echogenic particles and 16 (5%) with dense amniotic sludge, were recruited. Dense amniotic sludge was linked with early (13%) but not with late (0%) primary outcome ( P < 0.01). Two women with combined dense amniotic sludge and short cervix delivered 4 and 10 weeks later (at 20 and 25 weeks, respectively) and had a higher median amniotic lactate concentration than controls ( P < 0.05). A third woman with dense amniotic sludge at 15 weeks was diagnosed with a short cervix and an intra-amniotic infection at 22 weeks that was eradicated with intravenous antibiotics. Midtrimester dense amniotic sludge is associated with early PPROM and spontaneous PTB.
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