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.

Random-start ovarian stimulation in women desiring elective cryopreservation of oocytes.

The current study investigates the utility of random-start ovarian stimulation in women desiring elective oocyte cryopreservation. Women in the study cohort underwent random-start ovarian stimulation, and were subdivided based on the phase of the menstrual cycle that ovarian stimulation began, i.e. early follicular, late follicular or luteal phase. Women undergoing conventional cycle day (CD) 2/3 ovarian stimulation start were controls. A total of 1302 women were included - 859 (66.0%) conventional CD 2/3, 342 (26.3%) early follicular, 42 (3.2%) late follicular and 59 (4.5%) luteal ovarian stimulation starts. There was no difference in the demographics or baseline ovarian stimulation characteristics. The duration of ovarian stimulation (11 versus 9 days; P < 0.001) and total dosage of gonadotrophins administered (4095.5 versus 3155 IU; P < 0.001) was higher in the random-start group. The number of total and MII oocytes in the control and random-start groups was similar. A non-significant trend towards increased cycle cancellation was noted in the late follicular start group (7.1%). Study findings indicate the number of total and MII oocytes derived from random-start protocols initiated during any phase of the menstrual cycle is similar to conventional CD 2/3 ovarian stimulation start protocols in women desiring elective oocyte cryopreservation.

Severe ovarian hyperstimulation syndrome after combined GnRH-agonist and low-dose human chorionic gonadotropin trigger in a patient with a single kidney.

Ovarian hyperstimulation syndrome (OHSS) following gonadotropin-releasing hormone agonist (GnRH-a) trigger is rare. Here, we report a case of severe OHSS after combined GnRH-a and low-dose human chorionic gonadotropin (hCG) trigger in a patient with a single kidney. The patient is a 32-year-old women with a two-year history of infertility. The patient's history was significant for a single kidney, that is, she had donated a kidney to a family member three years ago. The patient underwent controlled ovarian stimulation (COS) for in vitro fertilization (IVF) and received a combined 2 mg GnRH-a and 1500 IU hCG ovulatory trigger. Estradiol (E2) levels on the day of and after the trigger were 3800 pg/mL and 4001 pg/mL, respectively. Four days after the trigger, the patient began experiencing nausea, abdominal distention and dyspnea, and her blood testing revealed hemoconcentration (hemoglobin: 16.9 g/dL; hematocrit: 51.0%) and an elevated creatinine level (1.16 mg/dL). Fresh embryo transfer was deferred. The patient was admitted to the hospital for fluid monitoring and prophylactic anticoagulation. Following inpatient management, her hemoglobin, hematocrit and creatinine levels normalized. The current report highlights that the systemic effects of OHSS can be accentuated in patients with preexisting renal disease or a single kidney.

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.

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.

The role of in-vivo and in-vitro maturation time on ooplasmic dysmaturity.

This study investigates whether the timing of in-vivo and in-vitro maturation influences ooplasmic dysmaturity. This is a retrospective comparison of intracytoplasmic sperm injection (ICSI) cycles (index cycles) complicated by complete fertilization failure (CFF) to cycles with successful fertilization in the same patient. The cycle following the index cycle was modified intentionally to increase fertilization. The times between human chorionic gonadotrophin (HCG) trigger and oocyte retrieval, HCG trigger and removal of cumulus cells, and HCG trigger and sperm injection were recorded. Fifteen patients were included. Compared with successful fertilization cycles, index (CFF) cycles showed a shorter time interval between HCG trigger and oocyte retrieval (2029.0 ± 16 versus 2195.0 ± 10 min; P < 0.001), HCG trigger and removal of cumulus cells (2201.4 ± 15 versus 2309.0 ± 23 min; P < 0.001) and oocyte retrieval and removal of cumulus cells (114.0 ± 13 versus 171.8 ± 15 min; P < 0.001). The interval between HCG trigger and ICSI was comparable between groups. Findings reveal novel patterns in time intervals between HCG trigger, oocyte retrieval, removal of cumulus cells and ICSI. Thus, modulating time intervals between HCG trigger, oocyte retrieval, removal of cumulus cells and ICSI to grant fertilization seems feasible.

Adjuvant gonadotrophin-releasing hormone agonist trigger with human chorionic gonadotrophin to enhance ooplasmic maturity.

This study investigates whether an adjuvant gonadotrophin-releasing hormone agonist (GnRHa) trigger with human chorionic gonadotrophin (HCG) improves fresh intracytoplasmic sperm injection (ICSI) cycle outcomes in patients with poor fertilization history after standard HCG trigger alone. This study compared 156 patients with <40% fertilization rate in a prior ICSI cycle with standard HCG trigger who underwent another ICSI cycle with a combined 2 mg GnRHa and 1500 IU HCG ovulatory trigger. There was no difference in the baseline demographics, ovarian stimulation outcomes or sperm parameters of the groups. More mature oocytes were retrieved in the combined trigger group compared with the HCG trigger group: 12 (9-14) versus 10 (7-12); P = 0.01. The fertilization rate in the combined trigger group (59.2%) was higher than the HCG group (35.3%); P = 0.01. The odds of clinical pregnancy and live birth were 1.8 and 1.7 times higher, respectively, when comparing the former group to the latter; P = 0.03. The results suggest that combined GnRHa and HCG trigger in ICSI cycles is a reasonable approach to increase oocyte maturity, specifically ooplasmic maturity, thereby increasing fertilization and improving ICSI cycle outcomes in patients with a history of poor fertilization after standard HCG trigger alone.

Cyst aspiration or GnRH antagonist administration for ovarian cysts detected at the start of fresh in vitro fertilization cycles.

The primary objective of this study is to investigate the effect of transvaginal ultrasonogram (TVUS)-guided cyst aspiration or gonadotropin releasing hormone antagonist (GnRH-ant) administration for the management of solitary ovarian cysts detected at the start of in vitro fertilization (IVF) cycles on the outcomes of the same cycles. This is a single-center, retrospective, cohort study of patients who had TVUS-guided cyst aspiration or GnRH-ant treatment for ovarian cysts detected at the start of IVF during a 5-year period. Four hundred and three patients met inclusion criteria: 41 (10.2%) underwent cyst aspiration and 362 (89.2%) were treated with GnRH-ant. There was no difference in the demographics or baseline IVF cycle characteristics of the two groups. Patients treated with GnRH-ant had a longer duration of ovarian stimulation (10.8 ± 3.45 days versus 9.05 ± 4.06 days, p = 0.003) and required higher gonadotropin doses (3887.7 ± 1097.8 IU versus 3293.7 ± 990.5 IU; p = 0.01) compared with the cyst aspiration group. There was no difference in the clinical pregnancy (43.9% versus 41.4%), spontaneous miscarriage (9.76% versus 8.01%) and live birth (34.1% versus 33.4%) rates between the groups. Our findings suggest that cyst aspiration is comparable to GnRH-ant administration for the management of solitary ovarian cysts detected at the start of IVF cycles.

Comparison of ovarian stimulation response in patients with breast cancer undergoing ovarian stimulation with letrozole and gonadotropins to patients undergoing ovarian stimulation with gonadotropins alone for elective cryopreservation of oocytes†.

The primary objective of this study is to compare the oocyte yield in breast cancer patients undergoing controlled ovarian stimulation (COS) using letrozole and gonadotropins with patients undergoing COS with standard gonadotropins for elective cryopreservation of oocytes. Odds ratios (OR) for the number of mature oocytes were estimated. Pregnancy outcomes for breast cancer patients undergoing frozen-thawed 2-PN embryo transfers (FETs) after oncologic treatment were also noted. 220 and 451 cycles were identified in the breast cancer and the elective cryopreservation groups, respectively. Patients in the former group had lower peak estradiol levels [464.5 (315.5-673.8) pg/mL] compared to the latter [1696 (1058-2393) pg/mL; p < 0.01]. More oocytes were retrieved in the breast cancer group (12.3 ± 3.99) compared to the elective cryopreservation group (10.9 ± 3.86; p < 0.01). The odds for mature oocytes with letrozole and gonadotropins was 2.71 (95% CI 1.29-5.72; p = 0.01). Fifty-six FETs occurred in the breast cancer group. The clinical pregnancy and live birth rates per FET cycle were 39.7%, and 32.3%, respectively. Our findings suggest that COS with letrozole and gonadotropins yield more mature oocytes at lower estradiol levels compared to COS with gonadotropins alone. Breast cancer patients undergoing FET after oncologic treatment have live birth rates comparable to age-matched counterparts.

5-millimeter Trocar-site Hernias After Laparoscopy Requiring Surgical Repair.

Trocar-site hernias are rare complications of laparoscopic surgery. Although trocar-site hernias occur more often at >10-mm sites, hernias can still develop at 5-mm sites after laparoscopy and can lead to serious complications. The primary objective of this review is to summarize the current medical literature pertaining to the clinical presentation and predisposing risk factors of trocar-site hernias at 5-mm sites after laparoscopy. A total of 295 publications were identified, 17 (5.76%) of which met the inclusion criteria. Twenty-seven patients with trocar-site hernias were identified after laparoscopic cases. The median age (interquartile range) for all adult patients with trocar-site hernias was 63 years (interquartile range, 39.5-66.5 years). Eight of the 18 patients (44.4%) undergoing gynecologic laparoscopy were parous although details of parity were not reported in most publications. Simple manual reduction or laparoscopic reduction with fascial closure (21 patients [84%]) was used more often compared with exploratory laparotomy (4 patients [16%], p < .001) to manage trocar-site hernias. There was no statistical difference in the location of trocar-site hernias (i.e., umbilical [14 patients, 56%] vs nonumbilical/lateral [11 patients, 44%], p = .12). Findings of this review suggest that increased operative times and excessive manipulation can extend 5-mm fascial incisions, thereby increasing the risk of trocar-site hernias. Parous women older than 60 years may have unrecognized fascial defects, which confer a higher risk of trocar-site hernias after laparoscopic surgery, even in the absence of incision manipulation or prolonged surgical duration. Such patients may benefit from closure of 5-mm fascial incisions although prospective data are required to validate the overall generalizability of this management strategy.

Routine Monitoring of Liver, Renal, and Hematologic Tests After Single- or Double-Dose Methotrexate Treatment for Ectopic Pregnancies After In Vitro Fertilization.

STUDY OBJECTIVE: To investigate the trends in liver function tests (LFTs), renal function tests (RFTs), and complete blood count (CBC) between day 1 and day 7 after single- or double-dose methotrexate (MTX) treatment for sonographically confirmed ectopic pregnancies. DESIGN: Single center, retrospective chart review (Canadian Task Force classification II-3). SETTING: University-affiliated center. PATIENTS: All patients with a sonographically confirmed ectopic pregnancy after fresh in vitro fertilization-embryo transfer cycles between January 2004 and June 2013 treated with MTX were included. INTERVENTIONS: Single- or double-dose MTX treatment. MEASUREMENTS AND MAIN RESULTS: LFTs, specifically alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, and total bilirubin levels, were measured on day of MTX administration (baseline) and 7 days later (day 7). Similar measurements of RFTs (blood urea nitrogen [BUN] and creatinine) and CBC (white blood cell [WBC] and platelets) were also performed. The change in LFTs, RFTs, and CBC (Δ) between baseline and day 7 was calculated for both single- and double-dose MTX protocols. Furthermore, the change in LFTs, RFTs, and CBC (Δ baseline vs day 7) for single- and double-dose MTX protocols were compared. Complete data was available for 107 patients: 89 (83.2%) and 18 (16.8%) patients received single- and double-dose MTX treatment, respectively. For either single- or double-dose treatment, no significant difference was found between baseline and day 7 ALT, AST, albumin, total bilirubin, BUN, creatinine, WBC, or platelet levels after MTX treatment. A comparison of post-treatment changes in LFTs, RFTs, and CBC (Δ baseline vs day 7) also showed no difference between single- and double-dose protocols. CONCLUSION: Our study suggests that repeating LFTs, RFTs, or CBC on day 7 after single- or double-dose MTX treatment for sonographically confirmed ectopic pregnancies may not be necessary in patients with normal baseline testing on day 1.

Effect of Methotrexate or Salpingectomy for Ectopic Pregnancy on Subsequent In Vitro Fertilization-Embryo Transfer Outcomes.

OBJECTIVE: To investigate the effect of methotrexate (MTX) or salpingectomy for ectopic pregnancy on the outcomes of subsequent in vitro fertilization (IVF)-embryo transfer (ET) cycles. DESIGN: Retrospective cohort study (Canadian Task Force Classification II-3). SETTING: Academic center. PATIENTS: All patients undergoing fresh IVF-ET between January 2004 and July 2013 after treatment of an ectopic pregnancy with MTX or salpingectomy in the preceding IVF-ET cycle were analyzed for potential inclusion. INTERVENTION: MTX or laparoscopic salpingectomy for an ectopic pregnancy followed by a subsequent IVF-ET cycle. MEASUREMENTS AND MAIN RESULTS: A total of 144 patients with sonographically confirmed ectopic pregnancies were identified during the study period. Of these, 107 (74.3%) patients were treated with MTX and 37 (25.7%) were treated with laparoscopic salpingectomy. Eighty-eight patients (82.2%) in the MTX group and 22 patients (59.4%) patients in the salpingectomy group underwent a subsequent IVF-ET cycle. There were no significant differences in demographic data or baseline cycle characteristics between the 2 groups. No difference was observed in basal follicle-stimulating hormone (FSH) level before and after MTX or salpingectomy treatment. Indicators of ovarian responsiveness, including total days of stimulation, total dosage of gonadotropins, and number of mature oocytes before and after either treatment, were comparable in the 2 groups. The number of doses of MTX (1 vs > 1) did not correlate with changes in ovarian response. The pregnancy outcomes, specifically live birth, were equivalent in the 2 groups. Comparing post-MTX cycles and post-salpingectomy cycles, patients in the latter group required higher doses of gonadotropins (+705 IU vs +221.5 IU; p < .01), although the number of mature oocytes remained similar in the 2 groups. CONCLUSION: Treatment of ectopic pregnancies with MTX or salpingectomy might not adversely affect ovarian reserve, ovarian responsiveness, or subsequent IVF cycle outcomes. However, in our study cohort, patients treated with MTX, those s treated with laparoscopic salpingectomy required higher gonadotropin doses in a subsequent cycle to attain the same number of mature oocytes.

Impact of elevated peak serum estradiol levels during controlled ovarian hyperstimulation on the birth weight of term singletons from fresh IVF-ET cycles.

PURPOSE: To investigate the impact of elevated serum estradiol (E2) levels on the day of hCG trigger on the birth weight of term singletons after fresh In Vitro Fertilization (IVF)-Embryo Transfer (ET) cycles. METHODS: Retrospective cohort study of all patients initiating fresh IVF-ET cycles resulting in live births between January 2004 and February 2013. The incidence of low birthweight (LBW) term singletons in patients with E2 levels on day of hCG trigger above or below the 95 % cutoff for E2 values in our clinic (3,069.2 pg/mL) was estimated. Multiple gestations and vanishing twin pregnancies were excluded. RESULTS: Two thousand nine hundred thirty-nine singleton live births were identified for inclusion. One hundred forty seven (5 %) and 2792 (95 %) live singleton births occurred in patients with peak E2 levels above and below 3,069.2 pg/mL, respectively. The overall incidence of term LBW was 5.4 % in the >3,069.2 pg/mL group compared to 2.4 % in the ≤3,069.2 pg/mL group (P = .038). An E2 level >3,069.2 pg/mL on the day of hCG administration was associated with increased odds of LBW term singletons (OR = 2.29; 95 % CI = 1.03-5.11). The increased odds remained unchanged when adjusting for maternal age (aOR = 2.29; 95 % CI = 1.02-5.14; P = .037), gestational age at delivery (aOR = 2.04; 95 % CI = 1.22-3.98; P = .025), and day 3 versus blastocyst transfer (aOR = 2.5; 95 % CI = 1.11-5.64; P = .023). CONCLUSIONS: Peak E2 level >3,069.2 pg/mL is associated with increased odds of LBW term singletons after fresh IVF-ET cycles. Conservative stimulation protocols aiming not to exceed an E2 level of 3,000 pg/mL may be advantageous for placentation and fetal growth if a fresh transfer is planned.

Prognostic value of growth of 4-cell embryos on the day of transfer in fresh IVF-ET cycles.

PURPOSE: To investigate the prognostic value of growth of 4-cell embryos on the day of transfer in determining clinical pregnancy and live birth rates after fresh in vitro fertilization (IVF)-embryo transfer (ET) cycles. METHODS: Retrospective cohort study of all patients between January 2008 and January 2013 initiating fresh IVF-ET cycles resulting in embryos that were not more than 4 cells 72 h after oocyte retrieval in the morning of their transfer. Patients were stratified into 2 groups based on whether embryos did or did not grow more than the 4-cell stage on the afternoon of ET. The odds of clinical pregnancy and live birth were considered as primary outcomes. Student's t-tests and Chi-square (χ2) tests were used as indicated, with logistic regression controlling for maternal age and number of embryos transferred. RESULTS: Three hundred forty three patients were identified for inclusion: 165 and 178 patients had 4-cell embryos with and without growth on the afternoon of ET, respectively. The demographic and baseline IVF cycle characteristics of the study cohort were comparable. Patients with embryo growth had higher clinical pregnancy (13.9 % vs. 4.49 %) and live birth (10.9 % vs. 3.37 %) rates compared to patients without embryo growth. This represented an overall increased odds of clinical pregnancy [Odds ratio (OR) = 3.44; 95 % Confidence Intervals (CI) 1.49-7.93; P = 0.004)] and live birth (OR = 3.51; 95 % CI 1.36-9.07; P = 0.01). The increased odds remained unchanged after adjusting for maternal age and number of embryos transferred. CONCLUSIONS: Transfer of 4-cell embryos 3 days after oocyte retrieval can result in clinical pregnancies and live births, albeit at a low rate. Growth of an embryo more than the 4-cell stage on the afternoon of ET may serve as a positive prognostic factor for IVF-ET cycle outcome.

Is ABO blood type associated with ovarian stimulation response in patients with diminished ovarian reserve?

PURPOSE: Recent studies have explored the relationship between ABO blood type and serum markers of ovarian reserve, specifically follicle-stimulating hormone (FSH) and anti-mullerian hormone (AMH). The primary objective of this study is to investigate whether there is an association between ABO blood type and ovarian stimulation response in patients with serum markers of diminished ovarian reserve (DOR). METHODS: This is a retrospective study of all patients undergoing controlled ovarian stimulation (COS) for in vitro fertilization (IVF) between May 2010 and July 2013. Patients were sub-grouped, a priori, based on serum AMH levels: ≤1 ng/mL, ≤0.5 ng/mL and ≤0.16 ng/mL. Within each sub-group, demographic, baseline IVF characteristics and COS response parameters based on ABO blood types were compared. The number of mature oocytes retrieved was considered the primary outcome. Analysis of variance (ANOVA) and Chi-square tests were used to compare means and percentages between ABO blood types within groups. RESULTS: Complete data was available for 2575 patients. The mean (± SD) age and BMI of the study cohort was 38.9 (±3.97) years, 23.4 (±5.91) kg/m(2), respectively. The distribution of ABO blood types in the cohort was as follows: 36.8 % (A), 6.56 % (AB), 17.3 % (B), and 39.3 % (O). The demographics and baseline IVF characteristics were comparable among patients with blood types A, AB, B, and O within each AMH group. Within each AMH sub-group, no difference was found in the total days of COS, total gonadotropins administered, peak estradiol level, or number of mature oocytes retrieved based on blood type. CONCLUSIONS: Our results suggest no association between ABO blood type and ovarian stimulation response in patients with DOR. The predictive value of ABO blood type in determining ovarian stimulation response in such patients is currently limited.

Ex vivo retrieval and cryopreservation of oocytes from oophorectomized specimens for fertility preservation in a BRCA1 mutation carrier with ovarian cancer.

OBJECTIVE: To report a case of ex vivo oocyte retrieval from oophorectomized specimens in a BRCA1 mutation carrier undergoing surgical staging for ovarian cancer. DESIGN: Video case report and literature review. SETTING: University-affiliated center. PATIENT(S): A 37-year-old single woman, gravida 0, with a known BRCA1 mutation, presented to her oncologist with a complex right ovarian mass and elevated CA-125 level. Ovarian cancer was suspected, and the patient consented to complete surgical staging. Although she desired to cryopreserve oocytes for fertility preservation, conventional oocyte retrieval was deemed unsafe because follicular puncture would compromise the integrity of the ovarian capsule, thereby increasing the risk of malignant cell spillage and cancer upstaging. INTERVENTION(S): Luteal-phase ovarian stimulation with gonadotropins and letrozole was performed. Surgical staging was initiated 34 hours after the administration of the ovulatory trigger. MAIN OUTCOME MEASURE(S): Ex vivo retrieval of oocytes from bilateral oophorectomized specimens under direct visualization at the time of surgical staging. RESULT(S): Seven mature oocytes were retrieved and vitrified. Concomitant surgical staging was completed. CONCLUSION(S): The present case highlights the feasibility of ex vivo or extracorporeal retrieval of mature oocytes from oophorectomized specimens in patients with ovarian cancer. By avoiding follicular puncture within the pelvic cavity, it minimizes the risk of malignant cell spillage and cancer upstaging.

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.

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.

Early spontaneous multiple fetal pregnancy reduction is associated with adverse perinatal outcomes in in vitro fertilization cycles.

The primary objective of this study is to investigate whether early spontaneous multiple fetal pregnancy reduction, also known as vanishing twin syndrome, is associated with adverse perinatal outcomes in fresh in vitro fertilization cycles. This is a retrospective cohort study of women with live singleton births with and without an early vanishing twin after fresh in vitro fertilization. Characteristics compared included incidence of preterm birth, overall birth weight, overall low birth weight, overall very low birth weight, and term low birth weight. In all, 4049 patients with live singleton births were included-853 and 3196 with and without a vanishing twin, respectively. The vanishing twin group had a lower overall birth weight compared to those without (3279.5 ± 369.9 vs 3368.6 ± 567.5 g; p < 0.01). Early vanishing twin was also associated with an increased odds of overall low birth weight (odds ratio: 1.75; 95% confidence interval: 1.36-2.25; p < 0.01) and increased odds of term low birth weight (odds ratio: 3.44; 95% confidence interval: 2.14-5.53; p < 0.01). Our study suggests that early vanishing twin is associated with lower overall birth weight and higher odds of overall low birth weight and term low birth weight in live singleton births after fresh in vitro fertilization.

Pretreatment of normal responders in fresh in vitro fertilization cycles: A comparison of transdermal estradiol and oral contraceptive pills.

OBJECTIVE: The aim of this study was to investigate the impact of pretreatment with transdermal estradiol (E2) compared to oral contraceptive pills (OCPs) on controlled ovarian stimulation (COS) response in normal responders undergoing fresh in vitro fertilization (IVF)-embryo transfer (ET) cycles. METHODS: A retrospective cohort study was performed of normal responders undergoing fresh IVF-ET cycles who received pretreatment with transdermal E2 versus OCPs prior to fresh IVF-ET. The total days of ovarian stimulation, total dosage of gonadotropins, total number of oocytes, and mature oocytes retrieved were noted. Pregnancy outcomes after ET were also recorded. RESULTS: A total of 2,092 patients met the inclusion criteria: 1,057 and 1,035 patients in the transdermal E2 and OCP groups, respectively. Patients in the OCP group had a longer duration of COS (10.7±1.63 days, p<0.01) than the E2 group (9.92±1.94 days). Patients in the OCP group also required higher cumulative doses of gonadotropins (2,657.3±1,187.9 IU) than those in the E2 group (2,550.1±1,270.2 IU, p=0.002). No statistically significant differences were found in the total and mature oocytes retrieved or in the rates of biochemical pregnancy, clinical pregnancy, spontaneous miscarriage, and live birth between the groups. CONCLUSION: Our findings suggest that compared to OCPs, pretreatment with transdermal E2 is associated with a shorter duration of ovarian stimulation and lower gonadotropin utilization, without compromising the oocyte yield or pregnancy outcomes in normal-responder patients undergoing fresh IVF.