Fragile X-Associated Diminished Ovarian Reserve and Primary Ovarian Insufficiency from Molecular Mechanisms to Clinical Manifestations

Fragile X syndrome (FXS), is caused by a loss-of-function mutation in the FMR1 gene located on the X-chromosome, which leads to the most common cause of inherited intellectual disability in males and the leading single-gene defect associated with autism. A full mutation (FM) is represented by more than 200 CGG repeats within the FMR1 gene, resulting in FXS. A FM is inherited from women carrying a FM or a premutation (PM; 55–200 CGG repeats) allele. PM is associated with phenotypes distinct from those associated with FM. Some manifestations of the PM are unique; fragile-X-associated tremor/ataxia syndrome (FXTAS), and fragile-X-associated primary ovarian insufficiency (FXPOI), while others tend to be non-specific such as intellectual disability. In addition, women carrying a PM may suffer from subfertility or infertility. There is a need to elucidate whether the impairment of ovarian function found in PM carriers arises during the primordial germ cell (PGC) development stage, or due to a rapidly diminishing oocyte pool throughout life or even both. Due to the possibility of expansion into a FM in the next generation, and other ramifications, carrying a PM can have an enormous impact on one’s life; therefore, preconception counseling for couples carrying the PM is of paramount importance. In this review, we will elaborate on the clinical manifestations in female PM carriers and propose the definition of fragile-X-associated diminished ovarian reserve (FXDOR), then we will review recent scientific findings regarding possible mechanisms leading to FXDOR and FXPOI. Lastly, we will discuss counseling, preventative measures and interventions available for women carrying a PM regarding different aspects of their reproductive life, fertility treatment, pregnancy, prenatal testing, contraception and fertility preservation options

Outcomes of Intracytoplasmic Sperm Injection Cycles for Complete Teratozoospermia: A Case-Control Study Using Paired Sibling Oocytes

Objective. To investigate the outcomes of intracytoplasmic sperm injection (ICSI) cycles where sibling oocytes from a single donor were split between two recipients based on strict sperm morphology.Methods. Retrospective cohort study. All ICSI cycles had one donor’s oocytes split between two recipients in a 1 : 1 ratio based on strict sperm morphology, that is, one male partner had morphology of 0% and the other had morphology of &gt;1%. Fertilization, positive hCG, clinical pregnancy, spontaneous miscarriage, and live birth rates of the aforementioned groups were compared.Results. The baseline characteristics of the two groups (n=103), including semen parameters of the male partners, were comparable. There was no difference in the fertilization rates when comparing the 0% group to the &gt;1% group (78.7% versus 81.6%;P=0.66). The overall positive hCG, clinical pregnancy, spontaneous miscarriage, and live birth rates for the 0% group were 61.2%, 49.5%, 10.7%, and 38.8%, respectively. The corresponding rates in the &gt;1% group were positive hCG (63.1%), clinical pregnancy (55.3%), spontaneous miscarriage (7.77%), and live birth (46.6%).Conclusions. The fertilization and pregnancy outcomes of ICSI cycles for strict sperm morphology of 0% versus morphology of &gt;1% are equivalent. These results can provide reassurance to couples undergoing ICSI for severe teratospermia.</jats:p

Perinatal Risks Associated with Early Vanishing Twin Syndrome following Transfer of Cleavage- or Blastocyst-Stage Embryos

Objective. To investigate whether the perinatal risks associated with early vanishing twin (VT) syndrome differ between cleavage- or blastocyst-stage embryo transfers (ET) in fresh in vitro fertilization (IVF) cycles. Methods. Retrospective, single-center, cohort study of IVF cycles with fresh cleavage- or blastocyst-stage ETs resulting in a live singleton birth. The incidence of preterm birth (PTB), low birth weight (LBW), and very low birth weight (VLBW) was compared between cleavage- and blastocyst-stage ET cycles complicated by early VT. Results. 7241 patients had live singleton births. Early VT was observed in 709/6134 (11.6%) and 70/1107 (6.32%) patients undergoing cleavage-stage and blastocyst-stage ETs, respectively. Patients in the blastocyst-stage group were younger compared to the cleavage-stage group. The cleavage-stage group had a similar birth weight compared to the blastocyst-stage group. There was no difference in the incidence of PTB (9.87% versus 8.57%), LBW (11.1% versus 11.4%), or VLBW (1.13 versus 1.43%) when comparing the cleavage-stage early VT and blastocyst-stage early VT groups, even after adjustment with logistic regression. Conclusions. Our study highlights that the adverse perinatal risks of PTB, LBW, and VLBW associated with early VT syndrome are similar in patients undergoing cleavage-stage or blastocyst-stage ETs during fresh IVF cycles