Factors affecting live birth rates in donor oocytes from commercial egg banks vs. program egg donors: an analysis of 40,485 cycles from the Society for Assisted Reproductive Technology registry in 2016-2018.

OBJECTIVE: To examine the differences in live birth rates (LBRs), with single embryo transfer (SET), using oocytes from program generated egg donors vs. commercial egg bank donors and other factors affecting LBRs using donor oocytes. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 40,485 in vitro fertilization cycles using donor oocytes reported to the Society for Assisted Reproductive Technology registry in 2016-2018. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth rate and cumulative LBR for SET using donor oocytes. RESULT(S): Multivariate results from the first SET from 19,128 cycles, including 15,429 from program generated egg donors and 3,699 from commercial egg banks, showed, when controlling for all other variables, the following: the LBR in the first SET cycle using commercial egg banks was 53.3% compared with 55.4% using program recruited egg donors (odds ratio [OR], 0.92); a reduction in the LBR with increasing recipient age, ages 40-44 years (OR, 0.80), 45-49 years (OR, 0.77), and >49 years (OR, 0.65); a steady decline in the LBR with increases in recipient body mass index above normal; and a steady increase in the LBR in association with >16 oocytes retrieved. Double embryo transfer increased the LBR (SET, 52%, vs. double embryo transfer, 58%) but also significantly increased the multiple pregnancy LBR, with 43% twins and 0.9% triplets. Blastocyst transfer had a higher LBR than cleavage stage embryos (52.5% vs. 39.5%). Intracytoplasmic sperm injection vs. conventional insemination when using fresh oocytes from program donors had similar LBRs. CONCLUSION(S): When performing in vitro fertilization using donor oocytes with SET, the LBR is affected by oocyte source, recipient age, recipient body mass index, stage of embryo at transfer, and number of oocytes retrieved.

Human granulosa-luteal cells initiate an innate immune response to pathogen-associated molecules.

The microenvironment of the ovarian follicle is key to the developmental success of the oocyte. Minor changes within the follicular microenvironment can significantly disrupt oocyte development, compromising the formation of competent embryos and reducing fertility. Previously described as a sterile environment, the ovarian follicle of women has been shown to contain colonizing bacterial strains, whereas in domestic species, pathogen-associated molecules are concentrated in the follicular fluid of animals with uterine infection. The aim of this study is to determine whether human granulosa-luteal cells mount an innate immune response to pathogen-associated molecules, potentially disrupting the microenvironment of the ovarian follicle. Human granulosa-luteal cells were collected from patients undergoing assisted reproduction. Cells were cultured in the presence of pathogen-associated molecules (LPS, FSL-1 and Pam3CSK4) for 24h. Supernatants and total RNA were collected for assessment by PCR and ELISA. Granulosa-luteal cells were shown to express the molecular machinery required to respond to a range of pathogen-associated molecules. Expression of TLR4 varied up to 15-fold between individual patients. Granulosa-luteal cells increased the expression of the inflammatory mediators IL1B, IL6 and CXCL8 in the presence of the TLR4 agonist E. coli LPS. Similarly, the TLR2/6 ligand, FSL-1, increased the expression of IL6 and CXCL8. Although no detectable changes in CYP19A1 or STAR expression were observed in granulosa-luteal cells following challenge, a significant reduction in progesterone secretion was measured after treatment with FSL-1. These findings demonstrate the ability of human granulosa-luteal cells to respond to pathogen-associated molecules and generate an innate immune response.

Angelman syndrome imprinting center encodes a transcriptional promoter.

Clusters of imprinted genes are often controlled by an imprinting center that is necessary for allele-specific gene expression and to reprogram parent-of-origin information between generations. An imprinted domain at 15q11-q13 is responsible for both Angelman syndrome (AS) and Prader-Willi syndrome (PWS), two clinically distinct neurodevelopmental disorders. Angelman syndrome arises from the lack of maternal contribution from the locus, whereas Prader-Willi syndrome results from the absence of paternally expressed genes. In some rare cases of PWS and AS, small deletions may lead to incorrect parent-of-origin allele identity. DNA sequences common to these deletions define a bipartite imprinting center for the AS-PWS locus. The PWS-smallest region of deletion overlap (SRO) element of the imprinting center activates expression of genes from the paternal allele. The AS-SRO element generates maternal allele identity by epigenetically inactivating the PWS-SRO in oocytes so that paternal genes are silenced on the future maternal allele. Here we have investigated functional activities of the AS-SRO, the element necessary for maternal allele identity. We find that, in humans, the AS-SRO is an oocyte-specific promoter that generates transcripts that transit the PWS-SRO. Similar upstream promoters were detected in bovine oocytes. This result is consistent with a model in which imprinting centers become DNA methylated and acquire maternal allele identity in oocytes in response to transiting transcription.