To develop an interpretable machine learning model for individualized gonadotropin dose selection during controlled ovarian stimulation. Historical, de-identified electronic medical record (EMR) data was collected from 4 IVF clinics in the United States. Records were filtered for autologous, non-canceled IVF retrievals, resulting in 7,977 cycles started between 2014 and 2020. A multiple linear regression model was developed with cross validation and recursive feature elimination to predict the number of eggs and mature (MII) eggs retrieved using baseline parameters available prior to start of treatment. The predictor variables were then used to create a patient similarity model based on K nearest neighbors (KNN), an interpretable machine learning technique. After identifying the best performing distance metrics, neighbor weights, and number of neighbors, the model was used to predict the number of eggs and MII eggs retrieved by calculating the weighted average from the set of K neighbors most similar to the patient of interest. The performance of the KNN model was compared to linear regression in terms of R-squared (R2) and mean absolute error (MAE). The KNN model was then used to (a) query the K most similar patients, and (b) identify the optimal gonadotropin dose in terms of highest number of MII eggs retrieved. We developed linear regression and KNN models using patient age, BMI, diagnosis, AMH, AFC, number of previous IVF cycles, and parity. KNN achieved highest performance using the Manhattan distance, 50-80 similar patients, and distance-based neighbor weighting. The KNN model outperformed linear regression for eggs retrieved (R2: 0.43 vs. 0.39, MAE: 4.84 vs. 4.98) and for MII eggs retrieved (R2: 0.39 vs. 0.35, MAE: 4.01 vs. 4.11). We then investigated the application of these models for gonadotropin dose selection. Linear models indicated that gonadotropin dose is negatively correlated with MII eggs, which may in part reflect that poor-prognosis patients are prescribed higher doses. In contrast, the KNN model showed that 22% of patients had a concave dose response curve, in which there was an optimal dose that maximized the number of MII eggs. We developed a patient similarity model using K nearest neighbors. The model showed better accuracy than linear regression for predicting eggs and MII eggs retrieved, and allowed the evaluation of which starting dose maximized the number of MII eggs retrieved, which is not possible with a linear model. Future work will optimize techniques for matching similar patients and extend the modeling for protocol selection.

BACKGROUND:Current professional society guidelines recommend genetic carrier screening be offered on the basis of ethnicity, or when using expanded carrier screening panels, they recommend to compute residual risk based on ethnicity. We investigated the reliability of self-reported ethnicity in 9138 subjects referred to carrier screening. Self-reported ethnicity gathered from test requisition forms and during post-test genetic counseling, and genetic ancestry predicted by a statistical model, were compared for concordance.RESULTS:We identified several discrepancies between the two sources of self-reported ethnicity and genetic ancestry. Only 30.3% of individuals who indicated Mediterranean ancestry during consultation self-reported this on requisition forms. Additionally, the proportion of individuals who reported Southeast Asian but were estimated to have a different genetic ancestry was found to depend on the source of self-report. Finally, individuals who reported Latin American demonstrated a high degree of ancestral admixture. As a result, carrier rates and residual risks provided for patient decision-making are impacted if using self-reported ethnicity.CONCLUSION:Our analysis highlights the unreliability of ethnicity classification based on patient self-reports. We recommend the routine use of pan-ethnic carrier screening panels in reproductive medicine. Furthermore, the use of an ancestry model would allow better estimation of carrier rates and residual risks.

Folliculogenesis in women is regulated largely by hormone signaling via the hypothalamic-pituitary-ovarian (HPO) axis. Hormone levels involved in HPO signaling vary depending on cycle timing, and can be affected by variables such as age, environment, and genetics. This study aimed to identify genetic variants that impact hormone signaling in women. Retrospective Clinical variables, including AMH and day 2/3 FSH, estradiol (E2), and progesterone (P4), were collected for 407 women. Genotype information was collected for 18 single nucleotide polymorphisms (SNPs) across 9 genes that were previously found to have associations with fertility markers. Statistical tests were run to measure the association between 1 hormone level and 1 SNP. Mann-Whitney U-tests were run when women were divided into 2 groups based on genotype; Kruskal-Wallis was run when women were divided into 3 groups based on genotype. A total of 62 hormone-SNP comparisons were made, 44 of which were not considered independent due to linkage disequilibrium. Adjusting for multiple hypothesis testing, a p-value of 0.001136 was considered significant. Informed consent was obtained. We found the FSHR p.S680N (rs6166) to be significantly associated with FSH levels (see Table 1). No other hormone-SNP associations were found to be significant. Our data confirmed the Ser allele leads to a less functional FSHR, resulting in a need for more FSH to have the same effect as FSHR with the Asn allele. Further, we see that the effect is dependent on how many copies of the 680Ser allele are present. This finding suggests a dose-dependent response. Future analyses in larger populations will be important for confirming the effect of 680Ser copies. This finding may help to refine treatment protocols for women pursuing ART treatments. However, the lack of other significant associations suggests the need for further analysis with larger sample size and more complex multivariate analysis.Tabled 1Statistical Analysis of Hormone-SNP AssociationsStatistical TestComparisonMean 1Mean 2Mean 3p-valueMann-WhitneySS v NN7.867.08N/A0.000221Mann-WhitneySS v SN + NN7.867.00N/A0.000489Mann-WhitneySS + SN v NN7.257.08N/A0.018567Kruskal-WallisSS v SN v NN7.866.957.080.001135 Open table in a new tab

Semen analysis (SA) may provide initial diagnosis of male factor infertility. The reliability of repeated SA producing valuable prognostic information for in vitro fertilization (IVF) success is inconsistent. The risk of failed fertilization is low (∼5%) and the financial and emotional costs of an unsuccessful IVF cycle are significant1. HBA is a sperm function test that provides qualitative assessment of sperm quality, maturity, and fertilization potential by measuring the proportion of sperm bound to hyaluronan. Semen samples with HBA scores of ≤65% are reported to be suboptimal and benefit from in vitro selection of hyaluronan-bound sperm in ICSI2. To determine whether HBA is a better predictor of fertilization success than the current IVF laboratory criteria (total motile normal morphology sperm count >20 million/mL on retrieval day). Retrospective review of all patients meeting the laboratory criteria for conventional insemination and having HBA on both diagnostic (d) and IVF sperm preparation (i) SA at a single fertility center between August 2013-2014. Pearson coefficient was calculated to determine correlation of SA parameters and conventional insemination fertilization rates (FR). 69 patient charts were reviewed with 8 patients having suboptimal FR (11%) including 3 failed and 5 low FR (defined as < 50% of mature oocytes). No correlation was found between dSA HBA score and FR (r= -0.005, 95% CI -0.242-0.232), or between the iSA HBA score and FR (coefficient -0.052, 95% CI -0.285-0.187). All failed fertilization and the majority of patients with low FR (60%) had elevated dHBA and iHBA values. Sperm morphology in dSA and/or iSA were not predictive of FR (r= -0.079, 95% CI -0.312 - 0.162; r= -0.126, 95% CI -0.368-0.133). Total motile count in the dSA and/or iSA were not predictive of FR (r= 0.115, 95% CI -0.125 - 0.343; r= -0.068, 95% CI -0.300-0.171). No correlation could be determined between dHBA or iHBA values. Total motile count, sperm morphology and HBA were not predictive of fertilization success or failure in conventional insemination IVF cycles. In addition, HBA values were not reproducible between SA samples and may not be a more accurate diagnostic sperm function test to predict fertilization potential.

Assessment of a universal SNP array based protocol, known as Karyomapping, as a PGD treatment strategy for patients requesting embryo testing for inherited disorders. Karyomapping utilizes a universal protocol, applicable to virtually all patients, for linkage-based PGD. It eliminates the need to develop and optimize patient-specific protocols, drastically reducing the waiting time for initiation of IVF treatment. This technology was previously validated using the gold-standard polymerase chain reaction methodology (with 100% concordance) and has proven to be highly efficient for even the most complex of cases, including those not feasible using conventional PGD methods.Among the 300 Karyomapping cases performed between December 2013 and May 2015, clinical outcome and follow-up data was collected for 223 PGD cycles with transferable embryos. Patients were referred from over 50 IVF centers in the USA. Embryos were biopsied at the blastocyst stage and frozen for transfer in subsequent cycle(s). Samples were whole genome amplified and analyzed using Karyomapping combined with direct mutation detection as needed and/or independent comprehensive chromosome screening (CCS) when requested (84% cases). The diagnostic rates were 98.7% for Karyomapping and 98.6% for CCS. The average numbers of embryos analyzed and eligible for transfer per cycle were 5.3 and 2.5 for PGD alone, and 6.2 and 2.3 for PGD+CCS. Batching of embryos prior to analysis was carried out for 11% of PGD+CCS cases (2% for PGD alone).The CCS improved clinical outcome. The implantation and clinical pregnancy rates were 70.5% (43/61) and 64% (34/53) for PGD+CCS cycles, versus 54.5% (6/11) and 55.6% (5/9) for PGD alone. Most transfers involved a single thawed blastocyst, except for ten patients (16%) who had two embryos transferred at once. The average maternal ages were 32.3 and 34.2 years for PGD and PGD+CCS, respectively. There are 13 live births and 36 ongoing pregnancies to date. Prenatal and perinatal testing was performed in four cases confirming PGD in all instances. The high clinical pregnancy rates were similar to outcomes achieved by the most successful in-vitro fertilization (IVF) programs. As lengthy patient-specific test developments were unnecessary, greater numbers of patients were treated with faster time to diagnosis, transfer and pregnancy. SNP arrays thus allow PGD laboratories to deal with the rapidly growing demand for embryo testing for inherited disorders. The application of Karyomapping with simultaneous CCS speeds up the testing process and further improves clinical outcomes.

More than fifty percent of normal 46, XX results of early miscarriage samples analyzed by traditional karyotype, are due to maternal cell contamination (Lathi et al. 2014). This error is eliminated by SNP microarrays with Parental Support™ (Natera). We sought to review the incidence, type, and origin of chromosomal abnormalities detected by SNP microarray technology in patients who experienced first trimester miscarriage. Retrospective analysis. A total of 150 first-trimester miscarriage samples were analyzed by SNP microarray at a single fertility clinic between January of 2012 and March of 2014. Miscarriage samples were obtained by suction dilatation and curettage under ultrasound guidance in the operating room. The products were paired with a sample of maternal blood and or a paternal blood, and sent for analysis. Patients were divided into four age groups <30, 30-34, 35-39, and ≥ 40. In addition, pregnancies were divided into whether they were spontaneous or via assisted reproductive technologies (ART). The overall rate of chromosomal abnormalities was 54%. Of the remaining specimens 34% were normal and 12% had maternal cell contamination (MCC). The aneuploidies were 86% maternal and 14% paternal in origin. ART pregnancies had similar rates of chromosomal abnormalities as spontaneous pregnancies, 51.5% vs. 59.6% respectively (X2=1.2, P=0.53). The rates of abnormalities in the four age groups were 42.3% vs. 59.3% vs. 57.1% vs. 84.4% respectively, with a significant increase above age 40 (X2=11.5, P=0.009). The most common abnormalities were trisomies 16 and 22. To our knowledge this is the largest study investigating the rate of chromosomal abnormalities detected by SNP microarrays in early pregnancy loss. Our study found that the rate of chromosomal abnormalities is similar between miscarriages in spontaneous pregnancies vs. those achieved by ART. Furthermore, we noted a significant increase in the rate of chromosomal abnormalities above maternal age of 40.

Objective: The purpose of this study was to determine what objective applicant characteristics increased the likelihood of successfully matching into a Reproductive Endocrinology and Infertility (REI) fellowship position. Methods: A prospective electronic survey was distributed to 130 applicants who participated in the 2011-2013 REI fellowship match. Applicants were asked questions regarding demographic/educational background, research experience, abstract/publication record, Council on Resident Education in Obstetrics and Gynecology (CREOG) exam scores, interview invitations, and match results. Statistical analysis was performed with Mann-Whitney U test to compare continuous and discrete ordinal variables, and Chi-square or Fisher's exact test to compare nominal variables, where appropriate. Results: Candidates that matched were younger (30.0 vs. 32.4 years old, p=0.02); otherwise, there were no other significant differences in candidates’ demographic background. Matched applicants had significantly more first author poster abstracts accepted (3.4 ± 0.4 vs. 1.1 ± 0.4, p=0.01). There was also a trend for matched applicants to have more publications accepted (3.3 ± 0.8 vs. 2.0 ± 1.0, p=0.14) and submitted (1.5 ± 0.4 vs. 0.8 ± 0.4, p=0.16). While candidates applied to a similar number of programs, matched applicants received more interview offers (17.1 ± 1.1 vs. 8.7 ± 2.1, p=0.002), attended more interviews (13.7 ± 0.7 vs. 8.1 ± 1.8, p=0.01), and ranked more programs (13.3 ± 0.7 vs. 8.1 ± 1.8, p=0.01). Conclusions: Research experience, particularly presenting poster abstracts as first author, was significantly associated with successful match into REI fellowship. There was also a trend for matched applicants to have more publications accepted and submitted at the time of the interview process.

Previous studies have shown a <7% oocyte to live born infant rate in fresh donor cycles. The purpose of this study was to evaluate the efficiency of cryopreserved donor oocytes compared to those from fresh donor cycles. Retrospective cohort study. Outcomes of all IVF cycles using previously cryopreserved donor oocytes from a single donor oocyte bank and performed at 19 partner ART institutions(1/2012-12/2013) were reviewed. These were compared to fresh donor IVF cycles performed at a large participant ART institution in 2012. Outcomes included cycle cancellation, number of oocytes thawed, number of cryopreserved supernumerary embryos, clinical pregnancy (CP: intrauterine gestational sac), ongoing pregnancy rates (OPR) and number of infants born. 626 cycles using thawed oocytes were initiated with a 93% continuation rate; 41% of embryo transfer (ET) cycles had supernumerary embryos for cryopreservation (n=238). Live birth rate/cycle was 51% (fresh) vs 44% (thaw)yielding 456 vs 332 infants. The twin rate was 14% vs 28% for fresh vs thaw donor cycles. Given an expected vitrified embryo to infant conversion rate of 35%, an additional 516 vs 150 infants are expected from these fresh and thaw cycles respectively. Final #infants/# thawed M2 oocytes was therefore (332+150)/3881 or 12.4% compared to (456+516)/8638 or 11.7% in fresh donor oocyte cycles. As frozen oocytes were stored in lots of 5-9, comparisons of ongoing pregnancy rate/thaw by number of oocytes thawed showed no significant differences (44.6% of 101 thaws of 5 vs 41.5% of176 thaws of 7 oocytes).Tabled 1Single Site Fresh Cycles 2012Multi-site Cryo-Bank Cycles (2012-2013)# Initiated Cycles1088626#M2 Oocytes86383881#M2 Oocytes surviving thaw (%)3337 (86%)# Cycles with ET (%)899 (83%)582 (93%)# Cancelled Cycles (%)132 (12%)44 (7%)CP/Cycle Initiated51%46%CP/ET Cycle61%50%OPR/Initiated cycle42%41%OPR/Transfer Cycle51%44%# Liveborn Infants456332Sets of Twins (%)60 (14%)71(28%)# Cycles with Vitrified Blasts (%)538 (60%)238 (41%)# Vitrified Blasts1476428Expected FET Delivery Rate35%35%Expected # FET infants516150#Infants/M2 Oocytes11.70%12.40% Open table in a new tab This study establishes the efficiency and viability of cryopreserved oocytes in IVF cycles. Low oocyte numbers per lot did not negatively impact overall outcomes therefore vitrified donor oocytes add ease of cycle timing and eliminate cancellations due to poor donor response.

To compare the clinical and multiple pregnancy rates in patients undergoing minimal-stimulation (mini-stim) with clomiphene citrate (CC) followed by a single injection of gonadotropin, to those receiving either CC or gonadotropin alone prior to intrauterine insemination (IUI). Retrospective chart review of 1,692 infertile couples that underwent ovulation induction between 2008 and 2011 in a single fertility clinic. Included were all women undergoing infertility treatment with ovarian stimulation followed by IUI. Ovarian stimulation protocols included daily 100 mg of CC alone, 100 mg of CC for 5 days followed by one 150 IU of gonadotropins (mini-stim), or daily gonadotropin injections. Couples were limited to a single treatment arm, and underwent between one and three cycles. Clinical and multiple pregnancies were defined by sonographic evidence of fetal cardiac activity. Pearson's ChiSquared was used to test for association between treatment protocols and outcome. The distribution of patients undergoing one, two, or three IUI cycles was similar irrespective of the treatment type. In patients younger than 35, the pregnancy rates for CC, mini-stim, and gonadotropins were 18.1%, 27.6%, and 31.7%, respectively (X2(2)=13.9, P=.0009). Patients aged 35-37 had pregnancy rates of 15.1%, 19.8%, and 15.0% (X2(2)=1.22, P=.5425). Patients between 38-40 of age had pregnancy rates of 8.7%, 17.6%, and 17.0% (X2(2)=2.63, P=.2677). Those older than 40 had pregnancy rates of 6.6%, 8.5%, and 5.3% (X2(2)=0.99, P=.6). Moreover, gonadotropins protocol had a significantly higher multiple pregnancy rate (25.6%) than both mini-stim (15.0%) and CC (11.7%), (X2(2)=7.29, P=.026). A mini-stim protocol with IUI achieves pregnancy rates similar to gonadotropins with IUI. In addition, mini-stim with IUI and CC with IUI protocols, had significantly lower multiple pregnancy rates than that of gonadotropins with IUI, in patients undergoing infertility treatments.

The Reproductive Endocrinology and Infertility (REI) fellowship match remains one of the most highly competitive processes among obstetrics and gynecology subspecialties. Between 2008 and 2012, the unmatched applicant rate ranged from 32.4% to 48.6%.a Several factors might influence an applicant’s chances of successfully matching into an REI fellowship position, such as prior research experience, publication record, and Council on Resident Education in Obstetrics and Gynecology (CREOG) scores. To our knowledge, no studies have been conducted analyzing factors that may affect an REI applicant’s likelihood to match. The purpose of this study is to determine what objective applicant characteristics may increase the likelihood of successfully matching into an REI fellowship position. One-hundred thirty-two applicants participated in the 2011-2012 REI Fellowship match. An electronic questionnaire was distributed to 80 applicants whose contact information was available. Applicants were asked questions regarding demographic information, educational background, research experience, abstract and publication record, exam scores, interview invitations, and match results. Mann-Whitney U test was used to compare continuous variables, and Chi-square or Fisher's exact test was used to compare nominal variables, where appropriate. Thirty-five applicants (43.8%) responded to the survey, of which 30 candidates matched. When divided into groups based on match outcome, candidates that matched were younger (29.6 vs. 31.8 years old, p=0.022), however there were no other significant differences in candidates’ demographic or educational background. Matched applicants had significantly more publications accepted (2.4 ± 0.3 vs. 0.8 ± 0.5, p=0.037), more first author publications accepted (1.5 ± 0.3 vs. 0.2 ± 0.2, p=0.033), more first author poster abstracts accepted (2.8 ± 0.4 vs. 0.8 ± 0.4, p=0.029), and higher CREOG scores (222.6 ± 1.9 vs. 210.2 ± 3.6, p=0.010). While candidates applied to a similar number of programs, matched applicants received more interview offers (17.7 ± 1.6 vs. 6.0 ± 0.8, p=0.001), attended more interviews (13.8 ± 0.9 vs. 5.8 ± 0.9, p=0.001), and ranked more programs (13.4 ± 1.0 vs. 5.8 ± 0.9, p=0.003). Obtaining high CREOG scores and publishing scientific articles and poster abstracts, particularly as first author, appear to be important factors in matching. Future studies of larger sample size incorporating a more balanced response rate from matched and unmatched candidates are needed to verify our findings and to examine factors that might be independently predictive of a successful match outcome. Nevertheless, this information may be useful to future applicants interested in pursuing a career in REI.

ObjectiveAdvancements in genomics allow for expanded, cost-effective, and high-throughput carrier screening. The American College of Medical Genetics (ACMG) recommends that phenotype and penetrance should be considered in selecting diseases for inclusion. Based on 1000 clinical samples screened, the selected diseases were classified according to these factors with the goal of improving transparency, pre- and post-test counseling and results disclosure protocols.DesignRetrospective study.Materials and MethodsRecombine's Comprehensive Carrier Screen for 978 mutations associated with 181 recessive diseases was performed on 1000 clinical referrals. Diseases were classified into 2 groups: high impact (significant effect on quality of life/reduced lifespan) and variable spectrum (less severe phenotype/lower penetrance). Informed consent to utilize de-identified data was obtained from all patients.ResultsTabled 1Most Common Variable Spectrum%1 inTOTAL98.91MTHFR Deficiency53.32Hemochromatosis: Type 124.14AMPD Deficiency15.37Duarte Galactosemia13.87Factor V Deficiency9.910Familial Mediterranean Fever: Mild9.810Congenital Nonclassical Adrenal Hyperplasia9.810Most Common High-Impact%1 inTOTAL39.93Familial Mediterranean Fever5.917Biotinidase Deficiency5.319Nonsyndromic Hearing Loss and Deafness4.920Polycystic Kidney Disease3.429Cystic Fibrosis3.231Glycogen Storage Disease: Type II1.281Alpha Thalassemia1.281 Open table in a new tab ConclusionWith the full panel, ∼99% of patients carry at least 1 mutation. More than 50% of samples carry MTHFR mutations. Considering only high-impact diseases, ∼40% of patients carry at least 1 mutation. Inclusion of mild disorders may create anxiety and logistical concerns for patients and physicians. This anxiety can be reduced with post-test genetic counseling, transparency about differences in severity between high-impact and variable spectrum diseases in all materials (pre-counseling, web-based & reports), and the ability to customize the disease panel. ObjectiveAdvancements in genomics allow for expanded, cost-effective, and high-throughput carrier screening. The American College of Medical Genetics (ACMG) recommends that phenotype and penetrance should be considered in selecting diseases for inclusion. Based on 1000 clinical samples screened, the selected diseases were classified according to these factors with the goal of improving transparency, pre- and post-test counseling and results disclosure protocols. Advancements in genomics allow for expanded, cost-effective, and high-throughput carrier screening. The American College of Medical Genetics (ACMG) recommends that phenotype and penetrance should be considered in selecting diseases for inclusion. Based on 1000 clinical samples screened, the selected diseases were classified according to these factors with the goal of improving transparency, pre- and post-test counseling and results disclosure protocols. DesignRetrospective study. Retrospective study. Materials and MethodsRecombine's Comprehensive Carrier Screen for 978 mutations associated with 181 recessive diseases was performed on 1000 clinical referrals. Diseases were classified into 2 groups: high impact (significant effect on quality of life/reduced lifespan) and variable spectrum (less severe phenotype/lower penetrance). Informed consent to utilize de-identified data was obtained from all patients. Recombine's Comprehensive Carrier Screen for 978 mutations associated with 181 recessive diseases was performed on 1000 clinical referrals. Diseases were classified into 2 groups: high impact (significant effect on quality of life/reduced lifespan) and variable spectrum (less severe phenotype/lower penetrance). Informed consent to utilize de-identified data was obtained from all patients. ResultsTabled 1Most Common Variable Spectrum%1 inTOTAL98.91MTHFR Deficiency53.32Hemochromatosis: Type 124.14AMPD Deficiency15.37Duarte Galactosemia13.87Factor V Deficiency9.910Familial Mediterranean Fever: Mild9.810Congenital Nonclassical Adrenal Hyperplasia9.810Most Common High-Impact%1 inTOTAL39.93Familial Mediterranean Fever5.917Biotinidase Deficiency5.319Nonsyndromic Hearing Loss and Deafness4.920Polycystic Kidney Disease3.429Cystic Fibrosis3.231Glycogen Storage Disease: Type II1.281Alpha Thalassemia1.281 Open table in a new tab ConclusionWith the full panel, ∼99% of patients carry at least 1 mutation. More than 50% of samples carry MTHFR mutations. Considering only high-impact diseases, ∼40% of patients carry at least 1 mutation. Inclusion of mild disorders may create anxiety and logistical concerns for patients and physicians. This anxiety can be reduced with post-test genetic counseling, transparency about differences in severity between high-impact and variable spectrum diseases in all materials (pre-counseling, web-based & reports), and the ability to customize the disease panel. With the full panel, ∼99% of patients carry at least 1 mutation. More than 50% of samples carry MTHFR mutations. Considering only high-impact diseases, ∼40% of patients carry at least 1 mutation. Inclusion of mild disorders may create anxiety and logistical concerns for patients and physicians. This anxiety can be reduced with post-test genetic counseling, transparency about differences in severity between high-impact and variable spectrum diseases in all materials (pre-counseling, web-based & reports), and the ability to customize the disease panel.

The Reproductive Endocrinology and Infertility (REI) fellowship match is highly competitive. To our knowledge, no studies have been done analyzing factors that may affect a REI applicant's likelihood to match. The purpose of this study is to determine what objective applicant attributes may increase the likelihood of successfully matching in a REI fellowship position. Survey. Sixty-seven applicants participated in the 2011 REI Fellowship match. An electronic questionnaire was distributed to 43 applicants whose contact information was available. Applicants were asked questions regarding demographic information, educational background, research experience, abstract and publication record, exam scores, interview invitations, and match results. Student's t-test and Mann-Whitney U test were used to compare continuous variables where appropriate, and Fisher's exact test was used to compare nominal variables. Twenty-two applicants (51.2%) responded to the survey and 16 candidates matched. When divided into groups based on match outcome, there were no significant differences in candidate's demographic or educational background. Both groups had similar abstract record, CREOG scores, and prior research experience; however, matched applicants had significantly more first author publications accepted (1.94±0.5 vs. 0.0±0.0, P=0.025) and submitted (1.1±0.2 vs. 0.0±0.0, P=0.03). While candidates applied to a similar number of programs, matched applicants received more interview offers (18.3±1.8 vs. 7.0±0.6, P=0.019), attended more interviews (14.6±1.2 vs. 6.7±0.9, P=0.013), and ranked more programs (14.4±1.2 vs. 6.7±0.9, P=0.016). The ability to submit and publish scientific articles as first author appears to be an important factor in matching. Future studies should be performed with a larger sample size to examine possible predictors in multivariate models. This information may be useful to future applicants interested in pursuing a career in REI.

Objective: To determine if outcomes after in vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI) using sperm from men with spinal cord injury (SCI group) differ from those of other etiologies of male factor infertility (non-SCI group). In men with SCI, to determine if IVF/ICSI outcomes differ with sperm obtained by penile vibratory stimulation (PVS group) versus electroejaculation (EEJ group).Design: Retrospective analysis.Setting: University medical center and major infertility center.Patient(s): Couples with male factor infertility due to SCI versus other etiologies.Intervention(s): PVS, EEJ, surgical sperm retrieval, and IVF/ICSI.Main Outcome Measure(s): Rates of fertilization, pregnancy, and live birth.Result(s): A total of 31 couples in the SCI group underwent 48 cycles of IVF/ICSI, and a total of 297 couples in the non-SCI group underwent 443 cycles of IVF/ICSI. The SCI group had lower fertilization rates but similar pregnancy and live birth rates compared with the non-SCI group. These rates, however, did not differ significantly when the PVS group was compared with the EEJ group.Conclusion(s): IVF/ICSI of sperm from men with SCI yield lower fertilization rates but similar pregnancy and live birth outcomes as IVF/ICSI of sperm from men with other etiologies of male factor infertility. Sperm collected by PVS versus EEJ in men with SCI appear to result in similar IVF/ICSI success rates. (Fertil Steril (R) 2011;96:562-6. (C) 2011 by American Society for Reproductive Medicine.)

Objective: To determine threshold beta-hCG levels predictive of an ongoing pregnancy (OP), live birth (LB), and multiple gestation (MG) in IVF cycles resulting from day-3 (D3) vs. day-5 (D5) embryo transfers (ET), to compare IVF cycle characteristics and pregnancy outcomes in D3 vs. D5 ET groups, and to assess the degree to which maternal characteristics and cycle parameters were predictive of higher beta-hCG levels.Design: Retrospective analysis.Setting: Infertility center.Patient(s): Women who had ET performed for IVF cycles between July 2004 and January 2010.Intervention(s): Embryo transfer performed on either D3 or D5 after oocyte fertilization.Main Outcome Measure(s): Beta-hCG on day 15 after oocyte fertilization.Result(s): Beta-hCG levels were significantly higher with D5 ET compared with D3 ETs (D3: 103.6 +/- 4.4 IU/L vs. D5: 198.0 +/- 10.6 IU/L), and a multivariate analysis demonstrated that D5 ET was a significant predictor of higher beta-hCG levels. The beta-hCG thresholds predictive of OP were 78 IU/L and 160 IU/L for D3 and D5 ET, which predicted OP in 96% and 91% of cases, respectively. Similarly, for LB, the beta-hCG thresholds were 94 IU/L (79% positive predictive value [PPV]) and 160 IU/L (88% PPV), and for MG were 250 IU/L (18% PPV) and 316 IU/L (34% PPV), respectively.Conclusion(s): Initial beta-hCG levels are dependent on the day of ET and are a reliable and highly predictive tool for OP outcomes. (Fertil Steril (R) 2011;96:1362-6. (c) 2011 by American Society for Reproductive Medicine.)

I. Three Accepted Classifications for Embryos........................................................... 6 A. An Embryo as a Person.....................................................................................6 B. An Embryo as a Potential Person....................................................................7 C. An Embryo as Property................................................................................7

To evaluate the post-thaw survival and the pregnancy outcomes of vitrified human blastocysts, a retrospective analysis was performed. A total of 213 blastocysts were thawed and transferred to 81 patients with 83% post-thaw survival, 31% clinical pregnancy, and 23% implantation rate per embryo. The clinical application of blastocyst vitrification with the cryoloop technique is effective based on the post-thaw survival and the pregnancy outcome.

A prospective study was performed in 24 premenopausal women to evaluate the gonadotropin dynamics of pharmacologic doses of transdermal estradiol-17-beta (E2) administered after bilateral oophorectomy. Patients were given 0.2-mg transdermal E2 patches for 2 weeks, followed by 0.1-mg patches for 4 weeks either immediately postoperatively (immediate estrogen replacement therapy [ERT] or beginning 12-14 days after surgery (delayed ERT). Serum gonadotropins and E2 levels were measured serially, and post-menopausal symptoms were prospectively recorded. Administration of 0.2 mg transdermal E2 immediately after surgery suppressed the post-castration rise in gonadotropins for at least 4 days, but LH and FSH levels did increase to the menopausal range after 2 weeks despite continued therapy. Sustained circulating levels of E2 with transdermal E2 therapy were comparable to follicular phase values. Vasomotor symptoms were well controlled by 0.2 mg of transdermal E2 in the majority of patients during the clinical trial. There was no significant estrogen-related morbidity despite the large doses used. Two patients had skin irritation at the patch site causing discontinuation of therapy. These data suggest that large doses of transdermal E2 can suppress gonadotropin levels only for a brief interval. We were unable to demonstrate any long-term alteration in the hypothalamic-pituitary set point for sensitivity to exogenous E2.

Because we previously found increased basal serum cortisol levels in women runners, we examined adrenocortical function in amenorrheic running women (AR), eumenorrheic running women (R), and normal nonexercising women (NC) in further detail. Mean 24-h urinary cortisol levels were significantly elevated (P less than 0.001) in six AR [45.1 +/- 7.2 (+/- SEM) micrograms/24 h] and eight R (38.5 +/- 6.9 micrograms/24 h) compared to four NC (13.9 +/- 2.8 micrograms/24 h). After adrenal suppression with 2 mg dexamethasone, integrated responses and absolute maximal elevations in serum cortisol levels in response to 10 micrograms/m2 exogenous ACTH (1-24) administered as an iv bolus dose, were not significantly different among six AR, six R, and six NC. This dose of ACTH results in maximal steroid release. The disappearance rates of cortisol (5 mg, iv) after dexamethasone suppression were similar in four AR, five R, and four NC and corresponded to a two-compartment model with mean half-lives of 4.9 and 93.8 min, respectively. Cortisol-binding globulin levels were also similar among the groups. These data document higher cortisol secretion and suggest increased ACTH secretion in running women.