Endometrial compaction before frozen euploid embryo transfer improves ongoing pregnancy rates.

OBJECTIVE: To assess whether the calculated difference in endometrial thickness from the end of the estrogen phase to the day of ET (after 6 days of P in hormonally prepared cycles) is associated with ongoing pregnancy rates in euploid frozen ETs (FETs). DESIGN: An observational cohort study. SETTING: Single tertiary care medical center. PATIENT(S): Ultrasound images from 234 hormonally prepared FET cycles were assessed. All the transfers were elective single ETs of a euploid embryo, post-preimplantation genetic testing for aneuploidy (PGT-A). INTERVENTION(S): Ultrasound measurements of peak endometrial thickness at the end of the estrogen phase and again after 6 days of P at the time of ET. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate in relation to the delta between endometrial thickness at the end of estrogen phase and at the time of ET. RESULT(S): We calculated the ongoing pregnancy rate in cycles where the endometrial lining decreased (compacted) after addition of P by 5%, 10%, 15%, and 20% and demonstrated a significantly higher pregnancy rate after all rates of compaction of the endometrial lining in comparison with cycles where the endometrial lining did not compact. The ongoing pregnancy rate in this cohort, after compaction of 15% or more, was 51.5%, compared with 30.2% in cycles where the endometrial lining did not compact. CONCLUSION(S): There is a significant correlation between endometrial lining compaction and ongoing pregnancy rate in FET cycles of euploid embryos. These findings help to explain why some euploid embryos may fail to implant.

Endometrial compaction (decreased thickness) in response to progesterone results in optimal pregnancy outcome in frozen-thawed embryo transfers.

OBJECTIVE: To evaluate whether the change in endometrial thickness between the end of the estrogen phase and the day of embryo transfer has an impact on the pregnancy rate in frozen-thawed embryo transfer (FET) cycles. DESIGN: Retrospective observational cohort study. SETTING: Single tertiary care medical center. PATIENT(S): Ultrasound images in 274 FET cycles were reviewed. All patients underwent endometrial preparation with the use of hormonal therapy. INTERVENTIONS(S): Ultrasound measurements of endometrial thickness at the end of the estrogen phase and the day of embryo transfer. MAIN OUTCOME MEASURE(S): The change in endometrial thickness and ongoing pregnancy rate. RESULT(S): We calculated the ongoing pregnancy rate in patients whose endometrial thickness decreased (compacted) after starting progesterone by 5%, 10%, 15%, or 20% compared with patients with no change or increased endometrial thickness. The ongoing pregnancy rate was significantly increased at all levels of compaction compared with no compaction. The ongoing pregnancy rate showed a significant increase with each decreasing quartile of change in thickness (increased percentage of compaction) in the progesterone phase compared with the estrogen phase. CONCLUSION(S): There is a highly significant inverse correlation between the ongoing pregnancy rate and the change of endometrial thickness between the end of estrogen administration and the day of embryo transfer.

Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging.

Female reproductive capacity declines dramatically in the fourth decade of life as a result of an age-related decrease in oocyte quality and quantity. The primary causes of reproductive aging and the molecular factors responsible for decreased oocyte quality remain elusive. Here, we show that aging of the female germ line is accompanied by mitochondrial dysfunction associated with decreased oxidative phosphorylation and reduced Adenosine tri-phosphate (ATP) level. Diminished expression of the enzymes responsible for CoQ production, Pdss2 and Coq6, was observed in oocytes of older females in both mouse and human. The age-related decline in oocyte quality and quantity could be reversed by the administration of CoQ10. Oocyte-specific disruption of Pdss2 recapitulated many of the mitochondrial and reproductive phenotypes observed in the old females including reduced ATP production and increased meiotic spindle abnormalities, resulting in infertility. Ovarian reserve in the oocyte-specific Pdss2-deficient animals was diminished, leading to premature ovarian failure which could be prevented by maternal dietary administration of CoQ10. We conclude that impaired mitochondrial performance created by suboptimal CoQ10 availability can drive age-associated oocyte deficits causing infertility.

Potential adverse effect of sperm DNA damage on embryo quality after ICSI.

BACKGROUND: Sperm DNA damage is prevalent amongst infertile men and has been shown to strongly impact adversely natural reproduction, intrauterine insemination-assisted reproduction and to a lesser degree IVF/ICSI fertilization. The objective of this study was to examine further the relationship between sperm DNA denaturation (DD) and reproductive outcomes after ICSI. METHODS: We evaluated infertile couples (n = 60) undergoing IVF/ICSI at a single centre. Sperm DD was assessed by flow cytometry analysis of Acridine Orange-treated sperm and expressed as the percentage of sperm with DD. Couples were sub-grouped according to sperm DD results: group 1: 0-15%; group 2: >15-30%; group 3: >30%. RESULTS: There were no differences between the three groups with regard to maternal age, sperm parameters, oocyte maturation, fertilization or pregnancy rates. Group 3 had a significantly higher rate of multinucleation among the embryo cohorts compared to either groups 1 or 2 (20% versus 10% and 8% respectively, P = 0.04). There was a statistically insignificant trend toward an increased spontaneous pregnancy loss rate in group 3 (P =0.50). CONCLUSION: Although we did not observe significant relationships between sperm DNA damage and either fertilization or pregnancy rates, the potential adverse effect of sperm DNA damage on embryo quality and spontaneous pregnancy loss is concerning.

Binucleated and micronucleated blastomeres in embryos derived from human assisted reproduction cycles.

This prospective sequential, cohort study examined the two most common multinucleation phenotypes observed in the authors' clinic, binucleated (BN) and micronucleated (MN) blastomeres, and included all intracytoplasmic sperm injection (ICSI) patients <40 years of age with at least one multinucleated embryo in the cohort as observed on day 2 of development. Eighty ICSI cycles of 560 consecutive cycles had multinucleated embryos (14.3%). Of the 80 cycles, 770 embryos were derived; 183 (23.8%) were observed to be multinucleated. Blastocyst rates were significantly higher with BN than MN embryos. MN embryos were more often derived from embryos with poor pronuclear morphology (41/81 = 50.6%). Transferred mononucleated sibling embryos from the BN group had an ongoing pregnancy rate of 48% (12/25) compared with 15.4% (4/26 from the group with MN embryos (P = 0.03). The implantation rate for sibling embryos from the BN group was higher than for those from the MN group. Fluorescence in-situ hybridization (FISH) analysis showed that BN embryos had normal blastomeres significantly more frequently than MN embryos (9/28 (32.1%) versus 1/27 (3.7%), P = 0.016). Time-lapse photography showed that the nuclei of both morphologies dissolved independently before the next mitotic division and that BN blastomeres definitely have two distinct nuclei. These observations indicate two diverse morphologies and causal mechanisms. Time-lapse photography showed that both were subject to independent dissolution of their nuclear membrane suggesting an asynchrony between the nuclei and a possible interruption in proper nuclear and cell division. Multinucleation should definitely be looked for during IVF assessment. Excluding these embryos from transfer is prudent practice.