Genetic profiling of azoospermic men to identify the etiology and predict reproductive potential.

PURPOSE: To identify germline mutations related to azoospermia etiology and reproductive potential of surgically retrieved spermatozoa, and to investigate the feasibility of predicting seminiferous tubule function of nonobstructive azoospermic men by transcriptomic profiling of ejaculates. MATERIALS AND METHODS: Sperm specimens were obtained from 30 men (38.4 ± 6 years) undergoing epididymal sperm aspiration for obstructive azoospermia (OA, n = 19) acquired by vasectomy, or testicular biopsy for nonobstructive azoospermia (NOA, n = 11). To evaluate for a correlation with azoospermia etiology, DNAseq was performed on surgically retrieved spermatozoa, and cell-free RNAseq on seminal fluid (n = 23) was performed to predict spermatogenesis in the seminiferous tubule. RESULTS: Overall, surgically retrieved sperm aneuploidy rates were 1.7% and 1.8% among OA and NOA cohorts, respectively. OA men carried housekeeping-related gene mutations, while NOA men displayed mutations on genes involved in crucial spermiogenic functions (AP1S2, AP1G2, APOE). We categorized couples within each cohort according to ICSI clinical outcomes to investigate genetic causes that may affect reproductive potential. All OA-fertile men (n = 9) carried mutations in ZNF749 (sperm production), whereas OA-infertile men (n = 10) harbored mutations in PRB1, which is essential for DNA replication. NOA-fertile men (n = 8) carried mutations in MPIG6B (stem cell lineage differentiation), whereas NOA-infertile individuals (n = 3) harbored mutations in genes involved in spermato/spermio-genesis (ADAM29, SPATA31E1, MAK, POLG, IFT43, ATG9B) and early embryonic development (MBD5, CCAR1, PMEPA1, POLK, REC8, REPIN1, MAPRE3, ARL4C). Transcriptomic assessment of cell-free RNAs in seminal fluid from NOA men allowed the prediction of residual spermatogenic foci. CONCLUSIONS: Sperm genome profiling provides invaluable information on azoospermia etiology and identifies gene-related mechanistic links to reproductive performance. Moreover, RNAseq assessment of seminal fluid from NOA men can help predict sperm retrieval during testicular biopsies.

A non-randomized clinical trial to determine the safety and efficacy of a novel sperm sex selection technique.

The desire to have offspring of a specific sex has a long history but has been particularly present with the appearance of assisted reproduction. However, embryo selection raises ethical concerns. Thus, several techniques to select sex-specific spermatozoa have been proposed but carry limitations. There are many variations of each technique, and some are time consuming and costly. Concerns about effectiveness and safety have also rendered many of them unappealing. Therefore, we propose a novel sperm sex selection technique (SST) that appears to be consistently safe and effective. A single-center, non-randomized clinical trial was designed. We included 1,317 couples, who were assigned to one of two groups: ICSI/PGTA or ICSI/PGTA+GS. Ejaculates from male partners of couples in the ICSI/PGTA+GS group (n = 105) were processed using SST to enrich spermatozoa for their desired sex. Standard sperm processing was carried out for couples undergoing PGT-A solely for aneuploidy (n = 1,212), comprising the ICSI/PGTA control group. To validate the efficacy of our technique, we performed an analysis on spermatozoa pre- and post-selection, followed by an assessment of the proportion of the conceptuses' sex to confirm clinical reliability. We also followed up on ICSI clinical outcomes and child/newborn health to establish the safety of our method. Our main outcome measures included the proportion of spermatozoa and embryos enriched for female and male sex, as well as embryo euploidy rates and ICSI clinical outcomes. These outcomes were compared between the two groups. For the ICSI/PGTA group (n = 1,212) (maternal age, 37.0±4yrs; paternal age, 39.1±6yrs), with ejaculated spermatozoa processed in the standard fashion, 2,303 ICSI cycles (1.2±1) yielded an 81.0% (14,375/17,737) fertilization. PGT-A results indicated a euploidy rate of 73.1% (n = 3,718) for female and 72.4% (n = 3,054) for male embryos. These couples achieved a 76.4% (699/915) implantation and 65.2% (597/915) clinical pregnancy rate, with 551 deliveries (48.5% female, 51.5% male). All 105 men in the ICSI/PGTA+GS group had sperm specimens with an equal sex distribution at baseline. Of them, 59 (paternal age, 40.9±6yrs) who desired female offspring obtained an 81.6% enrichment after SST. They underwent 73 ICSI cycles with their partners (maternal age, 37.9±4yrs), achieving a 77.3% (583/754) fertilization. This resulted in 79.1% (231/292) female embryos that generated a 79.3% (23/29) implantation rate, with 16 singleton deliveries of the desired female sex without major or minor congenital malformations. Forty-six couples (maternal age, 37.3±4yrs; paternal age, 40.7±6yrs) desiring male offspring obtained an 80.8% sperm sex enrichment. They underwent 50 ICSI cycles, achieving a 75.4% (462/613) fertilization and equivalent proportion of male embryos (223/280, 79.6%). Their implantation was 90.5% (19/21), with 13 singleton deliveries of healthy male offspring. Furthermore, 78.8% (182/231) of female and 66.4% (148/223) of male embryos from the ICSI/PGTA+GS cohort were euploid. These euploid rates were comparable to those from the ICSI/PGTA group. In couples undergoing ICSI with PGT-A, SST consistently enriched spermatozoa, resulting in a higher proportion of embryos and thus offspring of the desired sex. Moreover, SST did not impair the fertilization or embryo developmental competence of spermatozoa, nor did it affect offspring health. Trial registration: Clinicaltrials.gov NCT05500573.

Age-specific blastocyst conversion rates in embryo cryopreservation cycles.

RESEARCH QUESTION: What is the blastocyst conversion rate in embryo cryopreservation cycles, per year of female age? DESIGN: Retrospective cohort study including patients undergoing their first ovarian stimulation cycle at our center with planned freeze-all strategy January 1st, 2014-June 30th, 2020. Primary outcome was blastocyst conversion rate. Secondary outcomes included mature oocyte and fertilization rates. Patients were stratified by year of age to assess oocyte yield and embryo development outcomes. RESULTS: 3,362 patients were included. The median blastocyst conversion rate in patients ≤30 was 66.7% (interquartile range 50.0-86.6) and remained statistically comparable through age 40 with a significant decline among ages ≥41 (41-years: marginal effect (ME) -5.2% (-9.7 to -0.7); 42-years: ME -9.6% (-14.3 to -4.8); 43-years: ME -7.7% (-12.8 to -2.6); ≥44-years: ME -20.8% (-26.5 to -15.1)). For the entire cohort, the median mature oocyte rate was 81.8% and the median fertilization rate was 81.8%. The mature oocyte and fertilization rates remained statistically comparable for each year of age except age ≥44 which had a statistically significantly increased mature oocyte rate (ME 4.4% (1.3 to 7.5)) and statistically significantly decreased fertilization rate (ME -5.8% (-9.8 to -1.9)) CONCLUSIONS: In embryo cryopreservation cycles, the blastocyst conversion rate remained statistically comparable through age 40 followed by a statistically significant decline for patients ≥41; however, the mature oocyte and fertilization rates were not impacted by increasing age until age ≥44. Even in women ≥44, over 40% of fertilized oocytes developed to blastocyst. Overall, this information is useful when counseling patients during the embryo culture stage regarding predicted blastocyst yield.

Impact of FMR1 Pre-Mutation Status on Blastocyst Development in Patients Undergoing Pre-Implantation Genetic Diagnosis.

BACKGROUND/AIMS: The study aimed to investigate the impact of fragile X mental retardation 1 (FMR1) pre-mutation status on blastocyst development in patients undergoing pre-implantation genetic diagnosis (PGD). METHODS: Case-control study of patients <40 years undergoing PGD at blastocyst stage for FMR1 pre-mutation status. Age-matched patients undergoing PGD for other single gene disorders were considered controls. Blastocyst development, calculated per metaphase II (MII) oocyte retrieved and per 2 pronuclear (2PN) embryos, was compared between the 2 groups. Pregnancy outcomes after embryo transfer were also compared. RESULTS: Eighty-one and 791 patients were included in the FMR1 and control groups, respectively. FMR1 pre-mutation carriers had lower indicators of ovarian reserve, required higher gonadotropin doses, and had fewer MII oocytes retrieved. Mean blastocyst development per MII oocyte (12.6 vs. 29.4%; p < 0.001) and per 2PN embryos (21.5 vs. 41.7%; p < 0.001) was lower in the FMR1 group. An inverse correlation between the number of FMR1 CGG repeats and blastocyst development per MII oocyte (ρ = -0.63; p < 0.001) was observed. There was no difference in the rates of clinical pregnancy, spontaneous abortion, or live birth among the groups. CONCLUSION: Our study suggests lower rates of blastocyst development in patients with FMR1 pre-mutation status and an inverse correlation between the number of FMR1 CGG repeats and blastocyst development.

Arabian Peninsula ethnicity is associated with lower ovarian reserve and ovarian response in women undergoing fresh ICSI cycles.

PURPOSE: Recent studies have demonstrated that ethnicity can be an independent determinant of assisted reproductive technology (ART) outcomes. In this context, we investigate whether ART outcomes differ between Arabian Peninsula and Caucasian women. METHODS: This is a retrospective cohort study of women undergoing fresh intracytoplasmic sperm injection (ICSI)-embryo transfer (ET) cycles for male factor infertility. The study cohort was divided into 2 groups based on ethnicity-Arabian Peninsula or Caucasian. Ovarian reserve, ovarian response, and pregnancy outcomes were compared between the groups. A sub-analysis was performed between individual Arabian Peninsula nationalities for the same outcomes. A multiple linear regression model was used to assess the independent effect of ethnicity on ovarian response. RESULTS: Seven hundred sixty-three patients were included-217 (28.4%) Arabian Peninsula and 546 (71.6%) Caucasian. There was no difference in the mean age of the two groups; however, the former had a higher body mass index (28.5 ± 7.5 vs. 23.3 ± 5.7; P < 0.001). Although follicle stimulating hormone (FSH) levels and antral follicle counts (AFC) were within the normal range in both groups, Arabian Peninsula women had higher FSH levels (5.7 ± 2.5 vs. 4.9 ± 2.8; P = 0.001) and lower AFC (13.9 ± 4.7 vs. 16.5 ± 4.3; P < 0.001) when compared to Caucasian women. Women from the Arabian Peninsula also had a statistically lower number of mature oocytes retrieved (15.6 ± 6.8 vs. 14.1 ± 8.4; P = 0.01), despite requiring higher gonadotropin doses. Multiple linear regression reveled that Arabian Peninsula women had 2.5 (95% CI 2.1-3.9) less mature oocytes, even after controlling for confounders. A sub-analysis within the Arab cohort demonstrated that Qatari women had a higher yield of mature oocytes when compared to Emirati, Kuwaiti, and Saudi women. There was no difference in the rates of implantation, clinical pregnancy, or live birth when comparing individual Arabian Peninsula nationalities with each other or to Caucasians. CONCLUSIONS: Arabian Peninsula ethnicity is associated with lower ovarian reserve and ovarian response parameters in women undergoing their first ICSI-ET cycle.

Novel Fumarate Hydratase Mutation in Siblings With Early Onset Uterine Leiomyomas and Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome.

Hereditary leiomyomatosis renal cell cancer syndrome is an autosomal dominant disorder characterized by uterine and cutaneous leiomyomas and increased predisposition to renal cell carcinoma, papillary type II. The syndrome is caused by heterozygous mutations to the fumarate hydratase (FH) gene located on chromosome 1. Affected females generally present with early onset, atypical uterine leiomyomas and cutaneous findings, however, delays in diagnosis are very common in patients with isolated uterine findings. We present a case series of 2 sisters in their 20s who presented with isolated uterine leiomyomas and were found to carry a novel mutation for the fumarate hydratase gene. One patient was referred for treatment of infertility and recurrent miscarriages and the other was referred for acute symptomatic anemia due to myomas. Prompt diagnosis of hereditary leiomyomatosis renal cell cancer was made due to a high index of clinical suspicion based on early onset disease and familial clustering as well as characteristic pathologic findings on uterine leiomyoma surgical specimen. Timely diagnosis not only allowed for genetic counseling and renal cancer surveillance, but also for fertility counseling given the increased morbidity associated with uterine leiomyoma due to hereditary leiomyomatosis and renal cell cancer syndrome.

Gonadotropin-releasing hormone agonist trigger increases the number of oocytes and embryos available for cryopreservation in cancer patients undergoing ovarian stimulation for fertility preservation.

OBJECTIVE: To compare the oocyte and embryo yield associated with GnRH-agonist triggers vs. hCG triggers in cancer patients undergoing controlled ovarian stimulation (COS) for fertilization preservation. DESIGN: Retrospective cohort study. SETTING: Academic center. PATIENT(S): Cancer patients undergoing COS with letrozole and gonadotropins or gonadotropin-only protocols for oocyte or embryo cryopreservation. INTERVENTION(S): Gonadotropin-releasing hormone agonist or hCG trigger. MAIN OUTCOME MEASURE(S): Number of metaphase II (MII) oocytes or two-pronuclei (2PN) embryos available for cryopreservation were primary outcomes. Separate multivariate linear regression models were used to assess the effect of trigger type on the primary outcomes, after controlling for confounders of interest. RESULT(S): A total of 341 patients were included, 99 (29.0%) in the GnRH-agonist group and 242 (71%) in the hCG group. There was no difference in the baseline demographics of patients receiving GnRH-agonist or hCG triggers. Within the letrozole and gonadotropins group (n = 269), the number (mean ± SD, 11.8 ± 5.8 vs. 9.9 ± 6.0) and percentage of MII oocytes (89.6% vs. 73.0%) available for cryopreservation was higher with GnRH-agonist triggers compared with hCG triggers. Similar results were noted with GnRH-agonist triggers in the gonadotropin-only group (n = 72) (i.e., a higher number [13.3 ± 7.9 vs. 9.3 ± 6.0] and percentage of MII oocytes [85.7% vs. 72.8%] available for cryopreservation). Multivariate linear regression demonstrated approximately three more MII oocytes and 2PN embryos available for cryopreservation in the GnRH-agonist trigger group, irrespective of cancer and COS protocol type. CONCLUSION(S): Utilization of a GnRH-agonist trigger increases the number of MII oocytes and 2PN embryos available for cryopreservation in cancer patients undergoing COS for fertility preservation.

Association between ABO blood type and live-birth outcomes in single-embryo transfer cycles.

OBJECTIVE: To investigate the association between ABO blood type and live-birth outcomes in patients undergoing IVF with day 5 single-embryo transfer (SET). DESIGN: Retrospective cohort study. SETTING: University-affiliated center. PATIENT(S): Normal responders, <40 years old, undergoing their first IVF cycle with fresh SET. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live-birth rate was the primary outcome. Secondary outcomes were birth weight and gestational age at delivery. Univariate and multivariable logistic regression was used to examine the association between blood type and live birth, while controlling for confounders. Odds ratios (OR) with 95% confidence intervals (CI) for live birth were estimated. RESULT(S): A total of 2,329 patients were included. The mean age of the study cohort was 34.6 ± 4.78 years. The distribution of blood types was as follows: A = 897 (38.5%); B = 397 (17.0%); AB = 120 (5.2%); and, O = 1,915 (39.3%) patients. There was no difference in the baseline demographics, ovarian stimulation, or embryo quality parameters between the blood types. The unadjusted ORs for live birth when comparing blood type A (referent) with blood types B, AB, and O were 0.96 (95% CI, 0.6-1.7), 0.72 (95% CI, 0.4-1.2), and 0.96 (95% CI. 0.6-1.7), respectively. The adjusted ORs for live birth remained not significant when comparing blood type A to blood types B, AB, and O individually. No difference in birth weight or gestational age at delivery was noted among the four blood types. CONCLUSION(S): Our findings suggest that ABO blood type is not associated with live-birth rate, birth weight, or gestational age at delivery in patients undergoing IVF with day 5 SET.

Random Start Ovarian Stimulation for Oocyte or Embryo Cryopreservation in Women Desiring Fertility Preservation Prior to Gonadotoxic Cancer Therapy.

BACKGROUND: Women of reproductive age diagnosed with cancer are often interested in preserving gametes or reproductive tissue that would allow for future genetic parenthood. Preservation of fertility is often accomplished in young cancer patients via ovarian stimulation followed by oocyte or embryo cryopreservation. Conventional stimulation protocols, however, require 2-4 weeks to complete ovarian stimulation, oocyte retrieval and possible fertilization. Such a strategy may not be feasible in patients requiring urgent cancer treatment. Recent studies have highlighted that random start ovarian stimulation can be initiated irrespective of the phase of the menstrual cycle and is an attractive alternative to conventional ovarian stimulation. The primary aim of the current review is to discuss the feasibility and success of random start ovarian stimulation for oocyte or embryo cryopreservation in women desiring fertility preservation prior to gonadotoxic cancer therapy. METHOD: We performed a systematic review of medical literature published between January 2000 to June 2017 reporting the utility of random start ovarian stimulation for fertility preservation. Search terms included "fertility preservation," "cancer," "ovarian stimulation," "random-start ovarian stimulation," "embryo cryopreservation, and" "oocyte cryopreservation." Publications were included in this review only if patients underwent random start ovarian stimulation prior to cancer therapy. RESULTS: Nineteen publications were identified and perused by the authors. Most publications described the utility of random start ovarian stimulation in the setting of breast cancer. Radom-start stimulation was associated with a reduced time interval between ovarian stimulation initiation and oocyte or embryo cryopreservation. The yield of mature oocytes and their developmental potential into embryos was comparable between conventional and random-start protocols, albeit with higher gonadotropin doses in the latter. CONCLUSION: The current review suggests that random start ovarian stimulation can shorten the interval between ovarian stimulation and oocyte retrieval, with the yield of oocytes and embryos being comparable to conventional stimulation protocols. Thus, random start ovarian stimulation may serve as a better option for fertility preservation in patients requiring urgent cancer treatment.

Combined GnRH-agonist and human chorionic gonadotropin trigger improves ICSI cycle outcomes in patients with history of poor fertilization.

PURPOSE: The purpose of this study was to investigate the utility of a combined GnRH-agonist (GnRH-a) and human chorionic gonadotropin (hCG) trigger in improving ICSI cycle outcomes in patients with poor fertilization history after standard hCG trigger in prior ICSI cycles. METHODS: Retrospective cohort study. Patients with a fertilization rate of <20% in at least two prior ICSI cycles who subsequently underwent another ICSI cycle with hCG trigger were compared to those who underwent another ICSI cycle with a combined GnRH-a and hCG trigger. Oocyte maturity, fertilization, clinical pregnancy, and live birth rates were compared. A multiple linear regression model was used to explore the association between combined GnRH-a and hCG trigger (vs hCG trigger alone) and fertilization rate. RESULTS: A total of 427 patients with mean age of 37.3 ± 1.94 years and mean baseline fertilization rate of 17.9 ± 2.03% were included, of which 318 (74.5%) and 109 (25.5%) patients underwent a subsequent ICSI cycle with hCG and combined GnRH-a and hCG trigger, respectively. The baseline parameters of the male and female partner were similar. The mean fertilization rate in the combined trigger group was 16.4% (95% CI: 7.58-25.2%) higher than the hCG trigger group, even after adjustment for confounders. Patients in the combined trigger group had higher oocyte maturity (82.1 vs 69.8%), higher clinical pregnancy (27.5 vs 5.67%), and higher live birth rates (20.2 vs 3.46%) compared to the hCG trigger group. CONCLUSIONS: Combined GnRH-a and hCG trigger in ICSI cycles increase oocyte maturity, fertilization, clinical pregnancy, and live birth rates in patients with a history of poor fertilization after standard hCG trigger alone.

Temporal trends in minimally invasive myomectomy before and after the US Food and Drug Administration recommendation against electric morcellation.

OBJECTIVE: To investigate the temporal trends in minimally invasive myomectomy at one reproductive medicine center before and after the US Food and Drug Administration (FDA) recommendation against electric morcellation. METHODS: A retrospective chart review was undertaken of patients undergoing minimally invasive myomectomy between April 1, 2012, and April 30, 2016, at a center in New York. Temporal trends in laparoscopic myomectomy (LM), robot-assisted laparoscopic myomectomy (RAM), and laparoscopically assisted myomectomy (LAM), and intraoperative and postoperative outcomes before and after the April 2014 recommendation were compared. RESULTS: Minimally invasive myomectomy was performed in 73 patients. No difference was noted in the rates of minimally invasive myomectomy 2 years before (35/74 [47.3%]) and after (38/79 [48.1%]) the FDA's recommendation. The ratio of abdominal to minimally invasive myomectomy remained relatively constant before (68/59=1.15) and during the study period (80/73=1.10). There was a significant decrease in LM and RAM and a corresponding rise in LAM immediately after the recommendation (P<0.001). CONCLUSION: The rates of minimally invasive myomectomy before and after the FDA's recommendation did not differ, indicating that technical modifications to laparoscopic technique can allow surgeons to offer minimally invasive myomectomy to patients with symptomatic leiomyomas.

Ovarian Response and in Vitro Fertilization Outcomes After Salpingectomy: Does Salpingectomy Indication Matter?

STUDY OBJECTIVE: To investigate whether the ovarian response and pregnancy outcomes of patients undergoing in vitro fertilization (IVF) after salpingectomy are affected by the underlying indication for salpingectomy. DESIGN: Retrospective cohort study (Canadian Task Force classification II-3). SETTING: University-affiliated fertility center. PATIENTS: All patients age <37 years undergoing IVF within 12 months of laparoscopic salpingectomy. The underlying indication for laparoscopic salpingectomy in the study cohort was tubal ectopic pregnancy, unilateral or bilateral hydrosalpinx, or other reason (hematosalpinx or pyosalpinx), as confirmed by histopathology. INTERVENTIONS: IVF and embryo transfer (ET). MEASUREMENTS AND MAIN RESULTS: Surgical characteristics, demographics, ovarian stimulation parameters, total oocytes retrieved, fertilization rates, implantation rates, and clinical pregnancy rates were compared among the salpingectomy groups. Age- and time-matched patients undergoing their first IVF-ET cycle for male factor infertility, with no previous history of laparoscopy, served as controls. RESULTS: Of the 996 patients who underwent a laparoscopic procedure during the study period, 136 patients underwent unilateral salpingectomy for the following indications: 39 for ectopic pregnancy, 81 for unilateral hydrosalpinx, and 16 for other indications. Among these 136 patients, 29 in the ectopic pregnancy group, 75 in the unilateral hydrosalpinx group, and 10 in the "other" group underwent subsequent IVF-ET. Thirty-one patients underwent both bilateral salpingectomy and subsequent IVF-ET. There was no difference in the antral follicle counts before and after salpingectomy in all groups. There was a statistically significant difference in the mean duration of ovarian stimulation in the salpingectomy groups: ectopic pregnancy, 10.9 ± 2.15 days; unilateral hydrosalpinx, 9.56 ± 1.95 days; bilateral hydrosalpinx, 9.51 ± 2.01 days; "other", 9.89 ± 2.20 days; control, 9.76 ± 1.99 days. Similar trends were noted for total gonadotropins administered when comparing the ectopic pregnancy group (3375.9 ± 931.0 IU) with the remaining groups (unilateral hydrosalpinx, 2841.3 ± 1160.9 IU; bilateral hydrosalpinx, 2519.3 ± 1004.7 IU; "other", 2808.6 ± 990.1 IU; control, 2726.1 ± 1129.8 IU). There were no significant differences in the total number of oocytes retrieved, fertilization rate, implantation rate, or clinical pregnancy rate in the salpingectomy groups compared with controls. CONCLUSION: Although our findings indicate that patients undergoing IVF after salpingectomy for an ectopic pregnancy have a statistically significantly longer duration of stimulation and require higher gonadotropin doses compared with patients undergoing IVF after salpingectomy for other indications, these differences are of limited clinical significance, given that the total number of oocytes retrieved, implantation rate, and clinical pregnancy rate among the different salpingectomy groups are comparable to those in controls.

Increased odds of live birth in fresh in vitro fertilization cycles with shorter ovarian stimulation.

OBJECTIVE: To investigate the impact of prolonged ovarian stimulation on pregnancy outcomes in IVF cycles with fresh day 3 ET. DESIGN: Retrospective cohort study. SETTING: University-affiliated center. PATIENT(S): All patients initiating their first IVF cycle with fresh day 3 ET. Prolonged ovarian stimulation was defined as a duration of more than two standard deviations (95th percentile) for the study cohort (i.e., >13 days). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth rate was considered the primary outcome and was compared between patients undergoing ovarian stimulation for ≤13 days and >13 days. Odds ratios (OR) with 95% confidence intervals (CI) for all pregnancy outcomes after day 3 ET were calculated. The OR for live birth was adjusted using logistic regression. RESULT(S): A total of 6,410 and 339 patients underwent ovarian stimulation for ≤13 days and >13 days, respectively. There were no differences in the demographics or mean number of day 3 embryos transferred between the two groups. Ovarian stimulation ≤13 days was associated with increased odds of clinical pregnancy (OR 2.15, 95% CI 1.19-3.89) and live birth (OR 2.35, 95% CI 1.25-4.43). The increased odds for live birth in the ≤13-day group remained unchanged after logistic regression. Patients with clinical pregnancies in the >13-day group were younger (34.6 ± 4.91 years) compared with those who did not conceive (38.2 ± 4.72 years). CONCLUSION(S): Our findings suggest that ovarian stimulation ≤13 days is associated with increased odds of clinical pregnancy and live birth. In patients undergoing ovarian stimulation >13 days, younger age is associated with live birth.

Abdominal ectopic pregnancy with undetectable serum ß-human chorionic gonadotropin 9 days following blastocyst transfer.

With the availability of the highly sensitive ß-human chorionic gonadotropin (ß-hCG) assays, all pregnancies, including ectopic pregnancies (EP), are expected to have detectable serum ß-hCG at 4 weeks' gestation or 9 days following blastocyst transfer. To our knowledge, this is the first report of a woman who underwent in vitro fertilization, had undetectable serum ß-hCG 9 days after blastocyst transfer, and was then diagnosed with a ruptured abdominal EP and intra-abdominal bleeding 19 days later. This case highlights that the rise in serum ß-hCG might be delayed in abdominal EP compared to intrauterine pregnancy. This delay should raise the suspicion for EP, thus meriting close monitoring. Moreover, in the absence of menstruation, an undetectable serum ß-hCG 9 days post-blastocyst transfer should prompt ß-hCG measurement in 2-3 days to avoid the misdiagnosis of an EP.