Owen Davis’s research while affiliated with Weill Cornell Medicine and other places

Infertility is defined as the inability to conceive following 12 months of unprotected intercourse in instances where the female partner is younger than 35 years, and 6 months when she is 35 years or older. The basic, evidence-based infertility evaluation is outlined in this chapter, and an illustrative case is described. The fertility evaluation may be instituted at an earlier time point where specific pathology or reproductive dysfunction is suspected (irregular/absent menstrual cycles, known pelvic/peritoneal pathology, male factor including gonadotoxic exposure, testicular injury/surgery). Identification of etiologic factors guides appropriate therapeutic pathways. Where the etiology remains unexplained, empiric therapies are often successful.

We present a couple with history of complete fertilization failure, despite ICSI. Their treatment history, as well as previous semen analyses, led us to suspect a diagnosis of globozoospermia. A series of additional tests was therefore performed to further assess sperm function and characteristics, including chromatin compaction, DNA fragmentation, aneuploidy, presence of cytosolic factor, centrosome integrity, ultrastructural aspects, and the genomic profile of the male gamete. These advanced sperm function assays unanimously confirmed globozoospermia, and a subsequent ICSI cycle was performed in conjunction with our proprietary assisted gamete activation protocol, resulting in the live birth of two healthy baby girls.

Objective To treat couples with total fertilization failure (TFF) due to a combined oocyte- and sperm-related oocyte activation deficiency by optimizing oocyte response to chemical activation with calcium ionophore. Design Case report Setting Tertiary Hospital Patients Two couples with history of TFF after ICSI Intervention (s) To overcome oocyte-related OAD, extended in vivo/in vitro oocyte maturation was carried to enhance ooplasmic maturity; to address sperm-related OAD, AGT was performed to trigger oocyte activation. Main outcome measures Treatment cycle outcomes for the 2 couples undergoing ICSI with EOM and AGT. Results We identified 2 couples with TFF after ICSI due to combined factor of OAD confirmed by PLCζ expression and genomic assessment. Initial AGT treatment alone failed to enhance fertilization, suggesting superimposed oocyte dysmaturity prohibiting oocytes from responding to chemical stimuli. To address this complex form of OAD, in couple 1, 27 oocytes out of 34 retrieved presented normal metaphase II spindles after EOM; ICSI with AGT yielded a fertilization rate of 63.0% (17/27). All 17 zygotes were cryopreserved initially. Two embryos were thawed and transferred, yielding a monochorionic diamniotic twin pregnancy. Couple 2 underwent 3 ICSI cycles with EOM and AGT; 91.4% (32/35) of oocytes displayed normal metaphase II spindle and achieved an overall fertilization rate of 43.8% (14/32). A total of 12 blastocysts were cryopreserved. A single 46XY blastocyst was thawed and transferred, resulting in a singleton pregnancy. Conclusion Our study has demonstrated the usefulness of EOM by targeting spindle presence to enhance chemical responses to AGT.

Research Question Do women of racial minorities 40 years or older have similar reproductive and obstetric outcomes as White women undergoing IVF with fresh embryo transfer? Design This is a retrospective cohort study performed at a single academic university-affiliated center. The study population included women 40 years or older undergoing their first IVF cycle with fresh cleavage stage embryo transfer stratified by racial minority status: minority [Black or Asian] versus White. Clinical intrauterine pregnancy and live birth rate were the primary outcomes. Preterm delivery (< 37 weeks) and small for gestational age (SGA) were the secondary outcomes. Multivariable logistic regression controlling a priori for age and number of embryos transferred was performed. Odds ratios (OR) with 95% confidence intervals (CI) were estimated. Statistical significance was denoted by p < 0.05. Results A total of 2,050 cycles in women over the age of 40 were analyzed, 561 (27.4%) of which were performed in minority women and 1,489 (72.6%) in white women. After controlling for age and total number of embryos transferred, minority women were 30% less likely to achieve a pregnancy compared to their white (non-Hispanic) counterparts (aOR: 0.68, CI: 0.54-0.87). However, once pregnant, the odds of live birth were similar (aOR: 1.23, CI: 0.91-1.67). Minority women were significantly more likely to have lower gestational ages at time of delivery (38.5 versus 39.2 weeks, p = 0.009) and were more likely to have very preterm birth delivery 24-34 weeks (5.5 versus 1.0%, p = 0.021). There were no differences in the incidence of small for gestation infants delivered between groups. Conclusion Minority women of advanced reproductive age are less likely to achieve a pregnancy compared to white (non-Hispanic) women. However, once pregnancy is achieved, live birth rates are similar albeit with minority women experiencing higher rates of preterm delivery.

STUDY QUESTION Do women ≥40 years old without a male partner who utilize donor sperm have the same reproductive outcomes as those who utilize their partner’s sperm? SUMMARY ANSWER After controlling for relevant confounders, women ≥40 years old using donor sperm for IVF have significantly higher odds of having a live birth compared to those utilizing their partner’s sperm. WHAT IS KNOWN ALREADY Women who are unpartnered or in same-sex relationships are by definition not infertile, but may choose to conceive using donor sperm. It is not known how IVF outcomes are affected with the use of donor sperm compared to women utilizing their partner’s sperm, particularly at very advanced maternal ages. STUDY DESIGN, SIZE, DURATION This is a retrospective cohort study conducted at a university-affiliated center of women undergoing IVF with fresh embryo transfer between 2008 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were divided into two groups based on the ejaculated sperm source utilized: donor or partner sperm. Live birth rate was the primary outcome. Pregnancy rate was the secondary outcome. Multivariable logistic regression was performed and adjusted for age, the developmental stage of the embryo, and the number of embryos transferred. Unadjusted odds ratio (OR) and adjusted OR (aOR) with 95% CI for pregnancy and live birth were estimated. Statistical significance was denoted by P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE A total of 3910 cycles in women ≥40 years old were analyzed, of which 307 utilized donor sperm and 3603 utilized their partner’s sperm to conceive. In the univariate analysis, patients utilizing donor sperm were found to have similar pregnancy rates as those utilizing partner sperm (41.0 vs 39.8%, OR: 0.95, 95% CI: 0.75–1.20). After adjusting for age, the number of embryos transferred and the developmental stage of the embryos, the model estimates did not vary (aOR: 1.22, 95% CI: 0.95–1.56). Similarly, the univariate analysis for live birth did not demonstrate a difference between groups (19.2 vs 17.8%, OR: 0.91, 95% CI: 0.67–1.22). However, after a similar adjustment was made for confounders, the use of donor sperm was associated with statistically significant increased odds of live birth (aOR: 1.38, 95% CI: 1.01–1.88). LIMITATIONS, REASONS FOR CAUTION As with any retrospective study, the potential for residual confounding exists, despite attempts to control for this with regression modeling. WIDER IMPLICATIONS OF THE FINDINGS Women ≥40 years old who are unpartnered or in same-sex relationships can be counseled that their odds of a live birth are slightly better than women in heterosexual relationships utilizing their partner’s sperm. These findings serve to further refine and individualize counseling on the expected IVF outcomes for women in this population. STUDY FUNDING/COMPETING INTEREST(S) No funding was sought for this study. The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A.

Objective To describe the patient and cycle characteristics of women who undergo intrauterine insemination (IUI) immediately following an unsuccessful oocyte retrieval. Design Retrospective case-series. Setting University-affiliated center. Patient(s) Women who underwent an oocyte retrieval procedure in which no oocytes were retrieved followed by an IUI on the same morning. Interventions(s) None. Main Outcome Measure(s) Live birth rate, subsequent live birth rate Result(s) From 2011 to 2019, 63 cycles in 57 patients were identified. The mean (SD) age was 39.6 (4.6) years, and diminished ovarian reserve (94.7%) was the most common diagnosis. The median (IQR) number of previous IVF cycles in this cohort was 3 (1-7), with 56.1% having had at least one previous canceled IVF cycle. The majority of patients had undergone either ovarian stimulation (COH) (64.9%) or modified natural cycles (21.1%). The mean (SD) number of follicles >14 mm at the time of trigger was 1.9 (1.4), with 38.9% of patients manifesting a drop in their estradiol levels post-trigger. One pregnancy resulting in a live birth was identified (1.8%). For patients who underwent subsequent IVF cycles, 60.7% had at least one subsequent cancelled cycle. Three patients went on to achieve a live birth using autologous oocytes (6.5%). Conclusion(s) Same-day IUI for patients who have no oocytes retrieved is associated with a <2% chance of achieving a live birth. Of patients who attempt subsequent IVF cycles, nearly two-thirds will go on to have at least one subsequent cancelled cycle. In this poor-prognosis cohort, fewer than 10% will ultimately achieve a live birth using autologous oocytes.