Eve C. Feinberg

The zinc spark is an inorganic signature of human egg activation

Egg activation refers to events required for transition of a gamete into an embryo, including establishment of the polyspermy block, completion of meiosis, entry into mitosis, selective recruitment and degradation of maternal mRNA, and pronuclear development. Here we show that zinc fluxes accompany human egg activation. We monitored calcium and zinc dynamics in individual human eggs using selective fluorophores following activation with calcium-ionomycin, ionomycin, or hPLCζ cRNA microinjection. These egg activation methods, as expected, induced rises in intracellular calcium levels and also triggered the coordinated release of zinc into the extracellular space in a prominent “zinc spark.” The ability of the gamete to mount a zinc spark response was meiotic-stage dependent. Moreover, chelation of intracellular zinc alone was sufficient to induce cell cycle resumption and transition of a meiotic cell into a mitotic one. Together, these results demonstrate critical functions for zinc dynamics and establish the zinc spark as an extracellular marker of early human development.

Does methotrexate administration for ectopic pregnancy after in vitro fertilization impact ovarian reserve or ovarian responsiveness

OBJECTIVE To evaluate the effects of methotrexate (MTX) on the future fertility of women undergoing IVF by comparing ovarian reserve and ovarian responsiveness in the IVF cycle before and after an ectopic pregnancy (EP) treated with MTX. DESIGN Retrospective cohort study. SETTING Private reproductive endocrinology and infertility practice. PATIENT(S) Sixty-six women undergoing IVF before and after receiving MTX for an EP. INTERVENTION(S) Methotrexate administration and ovarian stimulation. MAIN OUTCOME MEASURE(S) Markers of ovarian reserve (day 3 FSH, antral follicle count), measures of ovarian responsiveness (duration of stimulation, peak E2 level, total dose of gonadotropins, number of oocytes retrieved, fertilization rate), and time from MTX administration to subsequent IVF cycle. RESULT(S) There were no differences after MTX administration in body mass index (BMI), FSH, or antral follicle count. A greater dose of gonadotropins was used in the cycle after MTX, but there were no differences in numbers of oocytes retrieved or high quality embryos transferred. As expected, there was a slight increase in age in the subsequent IVF cycle. The pregnancy rates (PR) were comparable to the average PRs within the practice when combining all age groups. CONCLUSION(S) Methotrexate remains the first line of therapy for medical management of asymptomatic EP and does not compromise ovarian reserve, ovarian responsiveness, or IVF success in subsequent cycles.

Racial disparities in in vitro fertilization outcomes

OBJECTIVE To evaluate the impact of race on in vitro fertilization (IVF) outcomes. DESIGN Retrospective analysis. SETTING Private practice. PATIENT(S) All women who underwent a first autologous IVF cycle at Fertility Centers of Illinois from January 2010 to December 2012. INTERVENTION(S) Information was collected on baseline characteristics, cycle parameters, and outcomes. Race was self-reported. MAIN OUTCOME MEASURE(S) Clinical intrauterine pregnancy and live birth rates. RESULT(S) A total of 4,045 women were included: 3,003 white (74.2%), 213 black (5.3%), 541 Asian (13.4%), and 288 Hispanic women (7.1%). A multivariable logistic regression was performed to control for confounders. Compared with white women, the adjusted odds ratio for clinical intrauterine pregnancy was 0.63 (95% confidence interval [CI] 0.44-0.88) in black women, 0.73 (95% CI 0.60-0.90) in Asian women, and 0.82 (95% CI 0.62-1.07) in Hispanic women. The adjusted odds ratio for live birth was 0.50 (95% CI 0.33-0.72) in black women, 0.64 (95% CI 0.51-0.80) in Asian women, and 0.80 (95% CI 0.60-1.06) in Hispanic women compared with white women. The spontaneous abortion rate was 14.6% in white women versus 28.9% in black women, 20.6% in Asian women, and 15.3% in Hispanic women. CONCLUSION(S) Black and Asian women had lower odds of clinical intrauterine pregnancy and live birth and higher rates of spontaneous abortion compared with white women. Further research is needed to better characterize the mechanisms associated with this racial disparity and to improve treatment options for black and Asian women.

Endometrin as luteal phase support in assisted reproduction

OBJECTIVE To compare clinical pregnancy rate (PR) and live birth rate (LBR) between Endometrin monotherapy versus Endometrin and P in oil combination therapy in assisted reproductive technology (ART) cycles. DESIGN Retrospective analysis. SETTING Large private practice. PATIENT(S) Patients undergoing autologous fresh IVF cycles, autologous frozen ET cycles, and fresh oocyte donor cycles were included for analysis. INTERVENTION(S) Endometrin as a single agent for luteal support, Endometrin monotherapy or Endometrin with P in oil used at least once every 3 days for luteal support, Endometrin combination therapy. MAIN OUTCOME MEASURE(S) Clinical PR and LBR. RESULT(S) A total of 1,034 ART cycles were analyzed. Endometrin monotherapy was used in 694 of 1,034 (67%) cycles and Endometrin combination therapy was used in 340 of 1,034 (33%) cycles. In all fresh cycles, clinical PR was not significantly different (IVF autologous: Endometrin monotherapy 46.9% vs. Endometrin combination therapy 55.6%; donor oocyte endometrin monotherapy 45.2% vs. Endometrin combination therapy 52.0%). Frozen ET cycles had a significantly higher clinical PR and LBR with combination therapy group compared with monotherapy (clinical PR 47.9% vs. 23.5%; LBR 37.5% vs. 17.3%). CONCLUSION(S) Endometrin monotherapy was sufficient for the P component of luteal support and provided high PRs for fresh cycles in both autologous and donor oocyte cycles. Clinical PR and LBR in frozen ET cycles were significantly improved with the addition of IM P to Endometrin therapy. This may reflect the fact that lesser quality embryos are transferred in frozen ET cycles, and more intense P support is required for comparable PRs.

The human oocyte preservation experience (HOPE) registry: Evaluation of cryopreservation techniques and oocyte source on outcomes

BackgroundThis prospective, Phase IV, multicenter, observational registry of assisted reproductive technology clinics in the USA studied outcomes of first cycles using thawed/warmed cryopreserved (by slow-freezing/vitrification) oocytes (autologous or donor).MethodsPatients were followed up through implantation, clinical pregnancy, and birth outcomes. The main outcome measure was live birth rate (LBR), defined as the ratio of live births to oocytes thawed/warmed minus the number of embryos cryopreserved for each cycle, averaged over all thawing cycles. Clinical pregnancy rate (CPR) was also evaluated, and was defined as the presence of a fetal sac with heart activity, as detected by ultrasound scan performed on Day 35–42 after embryo transfer.ResultsA total of 16 centers enrolled 204 patients; data from 193 patients were available for analyses. For donor oocytes, in the slow-freezing (n = 40) versus vitrification (n = 94) groups, respectively, CPR and LBR were significantly different: 32.4% versus 62.6%, and 25.0% versus 52.1%; outcomes from Day 3 transfers did not differ significantly. For vitrified oocytes, in the autologous (n = 46) versus donor (n = 94) group, respectively, CPR and LBR were significantly different: 30.0% versus 62.6% and 17.4% versus 52.1%. This was largely due to a significant difference in CPR with Day 5/6 transfers.ConclusionsIn two subgroup data analyses, in women who received cryopreserved oocytes from donors, CPR and LBR were significantly higher in cycles using oocytes cryopreserved via vitrification versus slow-freezing, reflecting differences in methodologies and more Day 5/6 transfers; in women who received vitrified oocytes, CPR and LBR were significantly higher in cycles using donor versus autologous oocytes with Day 5/6 transfers.Trial registrationClinicalTrials.gov: NCT00699400. Registered June 13, 2008.

Tests used in the diagnostic evaluation of infertility: from ubiquitous to obsolete

The only true wisdom is in knowing you know nothing. -Socrates.

Advances in cryopreservation: we are not frozen in time

Life is like riding a bicycle, to keep your balance you must keep moving. -Albert Einstein.

Ovarian hyperstimulation: past, present, and future

The good physician treats the disease; the great physician treats the patient who has the disease. -William Osler.

The relationship between recurrent pregnancy loss and the male contribution

Judge a man by his questions rather than his answers. -Voltaire.