Insulin-like growth factor-1 and soluble FMS-like tyrosine kinase-1 prospectively predict cancelled IVF cycles.

PURPOSE: To identify biomarkers that prospectively predict IVF cycle cancellation. METHODS: In this prospective study, sera were obtained prior to any intervention, from women about to undergo an IVF cycle. The sera were assayed by ELISA for levels of insulin-like growth factor (IGF)-1, IGF-2, IGF binding protein (BP)-1, and soluble fms-like tyrosine kinase (sFLT-1). The cancellation or progression of the IVF cycle was subsequently obtained by chart review. Associations between serum components and outcome were analyzed by the Mann-Whitney test. Receiver operator curves were constructed to evaluate the strength of the correlations between biomarkers and cycle cancellation, as assessed from the area under the curve (AUC). RESULTS: A total of 205 women were included. Twenty-seven (13.2%) cycle cancellations due to poor response were recorded. Women with a cancelled cycle had reduced anti-Mullerian hormone (AMH) values (p < 0.001) and antral follicle count (p = 0.003). There were no significant differences between the two groups with regard to age and BMI. Median concentrations of IGF-1 and sFLT-1 were elevated in sera from women whose IVF cycles were cancelled as compared to those with ongoing cycles (p = 0.015 and p < 0.001, respectively); AUC for IGF-1 and sFLT-1 were 0.67 and 0.75, respectively. Concentrations of sFLT-1 remained significantly higher in patients with cancelled cycles even after controlling for AMH levels. There were no differences in IGF-2 and IGFBP-1 levels between the two groups. CONCLUSIONS: Measurement of circulating IGF-1 and sFLT-1 levels prior to initiation of an IVF cycle has the potential to identify women whose cycles have an increased likelihood to be subsequently cancelled.

High proportion of immature oocytes in a cohort reduces fertilization, embryo development, pregnancy and live birth rates following ICSI.

RESEARCH QUESTION: Ooplasmic maturity has been studied for some time, but remains poorly defined. This study aimed to evaluate metaphase II (MII) oocyte competence in terms of fertilization, embryo development and cycle outcomes, according to the oocyte maturity ratio. DESIGN: Couples treated by intracytoplasmic sperm injection (ICSI) between 1993 and 2017 with female partners ≤35 years old were included. Cycles were divided into four groups according to proportion of MII oocytes at the time of retrieval: optimal (76-100%), adequate (51-75%), partial (26-50%) and minimal (1-25%). RESULTS: A total of 7672 ICSI cycles (optimal: 4838; adequate: 2252; partial: 518; minimal oocyte maturity: 64) were included, in which 95,667 MII oocytes were injected using ejaculated spermatozoa. The decreasing proportion of MII significantly reduced normal fertilization (two pronuclei) (78.9% to 71.3%; P < 0.0001) with a corresponding increase in digynic three-pronuclei that rose from 2.6% in the optimal group to 4.7% in the minimal group (P = 0.003). Implantation (33% to 17%; P < 0.0001), clinical pregnancy (63.6% to 37.5%; P < 0.0001) and live birth rates (49.2% to 26.6%; P < 0.0001) were affected by the decreasing proportion of MII oocytes. CONCLUSIONS: A high proportion of immature sibling oocytes in the retrieved cohort affects the fertilization rate and embryo developmental competence of MII inseminated oocytes, clinical pregnancy and live birth rates, suggesting that, in addition to nuclear maturity, ooplasmic and membrane maturity are required for developmental competence of MII oocytes. These findings may provide guidance toward ovarian stimulation protocols aimed at achieving a greater proportion of MII oocytes, leading to higher fertilization rates and better pregnancy outcomes.

BRCA carriers have similar reproductive potential at baseline to noncarriers: comparisons in cancer and cancer-free cohorts undergoing fertility preservation.

OBJECTIVE: To investigate whether BRCA carriers with and without malignancy have decreased ovarian reserve at baseline compared with BRCA noncarriers. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): Seven-hundred and ninety-five oocyte cryopreservation patients, comprising BRCA carriers with and without malignancy (n = 57) and BRCA noncarriers (n = 738). INTERVENTION(S): Fertility preservation with oocyte cryopreservation. MAIN OUTCOME MEASURE(S): Antral follicle count (AFC), antimüllerian hormone (AMH) concentration, day-3 follicle-stimulating hormone (FSH) level, number of harvested oocytes, and number of mature/cryopreserved oocytes. RESULT(S): In the cancer cohort we compared BRCA-positive breast cancer (n = 38) with BRCA-negative breast cancer (n = 53) and with non-breast-cancer malignancies (n = 85). In the cancer-free cohort we compared BRCA carriers (n = 19) with women undergoing elective egg freezing (n = 600). We also compared the BRCA1 (n = 31) versus the BRCA2 carriers (n = 18). The patients' mean ages were 32.4 ± 3.6 years and 35.5 ± 4.3 years in the BRCA carrier and noncarrier cohorts, respectively. BRCA status was associated with a higher day-3 FSH level in the cancer cohort, but we found no changes in the other outcomes compared with the BRCA-negative cancer groups. BRCA carriers without cancer exhibited a higher AFC and number of mature oocytes compared with the patients undergoing planned egg freezing. Overall (cancer and cancer-free cohorts), the BRCA carriers had an increased AFC (15.5 ± 4.6 vs. 12.6 ± 5.7) and number of mature/cryopreserved oocytes (14.0 ± 7.9 vs. 10.4 ± 6.9) compared with the BRCA noncarriers but had no differences in other outcomes. CONCLUSION(S): BRCA carriers with and without malignancy exhibit comparable ovarian reserve and responses to ovarian stimulation compared with women with BRCA-negative cancers and cancer-free controls.

Does maternal age at retrieval influence the implantation potential of euploid blastocysts?

BACKGROUND: Age-related decline in reproductive potential is mainly due to the increased incidence of aneuploidy. Furthermore, 2 recent studies have shown that euploid embryos of older women may have a lower implantation potential compared to those of younger women, suggesting that aging might compromise embryos beyond their ploidy status. However, the inherent limitations of these studies preclude solid conclusions. OBJECTIVE: The aim of this study was to determine whether maternal age at retrieval affects the implantation potential of euploid blastocysts. MATERIALS AND METHODS: This is a retrospective cohort study that was conducted at an academic medical center. Patients who underwent frozen-thawed euploid embryo transfers (FET) between 2013 and 2016 were included. Cycles were divided into the following 5 age groups: <35, 35-37, 38-40, 41-42, and >42 years of age. Blastocysts were assessed before biopsy and assigned the following morphological grades: excellent (3-6AA), good (3-6AB, 3-6BA), average (2-6BB), and poor (3-6BC, 3-6CB, 3-6CC). The main outcome measures were implantation (IR) and live birth (LBR) rates. Both χ2 and Fisher exact tests were used to compare categorical variables. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and controlled for confounders. RESULTS: A total of 785 FET cycles (870 blastocysts) were included. Excellent-quality blastocysts were associated with a significantly higher LBR compared with good-quality (78.8% vs 63.8%), average-quality (78.8% vs 54.2%), and poor-quality (78.8% vs 28.3%) counterparts. Poor-quality embryos yielded a higher spontaneous abortion (SAB) rate compared with average-, good-, and excellent-quality blastocysts (25.0%, 9.0%, 6.9%, and 2.4%, respectively). Embryos biopsied on day 5 had a significantly higher LBR compared with those biopsied on day 6 (60.0% vs 46.6%). The 5 age groups (<35, 35-37, 38-40, 41-42, and >42 years) had comparable IRs (56.5%, 52.9%, 55.4%, 59.1%, and 71.4%, respectively), LBRs (55.1%, 51.3%, 53.5%, 52.4%, and 61.9%, respectively), and SAB rates (8.8%, 7.9%, 8.3%, 14.3, and 13.3%, respectively). Older women had fewer euploid embryos, but they were of comparable morphology and developed at a similar rate to the blastocyst stage as compared to those of younger women. CONCLUSION: Maternal age at retrieval influences the number of euploid embryos; however, contrary to previously published studies, it does not affect their implantation potential. The morphodynamic characteristics of embryos, as reflected by blastocyst morphology and speed of development, are critical for selecting among euploid embryos.

IL-1ß predicts IVF outcome: a prospective study.

PURPOSE: Retrospective cohort studies have shown a relationship between maternal serum interleukin-1ß (IL-1ß) and interleukin-1 receptor antagonist (IL-1Ra) levels and in vitro fertilization (IVF) cycle outcome. The objective of this investigation was to explore the correlation between serum IL-1ß and/or IL-1Ra levels obtained prospectively and IVF outcomes. METHODS: Sera from 205 women were collected just prior to initiation of their IVF cycle, at the time of human chorionic gonadotropin administration, day 24 of IVF cycle, day 28, and day 35. Sera were analyzed for IL-1ß and IL-1Ra using commercially available ELISA kits. Cycle outcomes were followed prospectively. Data were analyzed using Friedman analysis of variance by ranks and chi-square analysis. RESULTS: Among women with a viable pregnancy, IL-1ß serum levels increased over time for those that proceeded to deliver or had an ongoing pregnancy. There was no increase in serum levels for those with subsequent pregnancy loss. Of the women that had an embryo transfer, detectable IL-1ß levels at the start of the cycle were associated with successful IVF outcome (p = 0.027). Of women with a positive pregnancy test, undetectable IL-1ß at the start of the cycle were associated with subsequent pregnancy loss (p = 0.046). For all IL1-Ra serum analysis, there were no significant results. CONCLUSIONS: The increasing levels of IL-1ß over time are consistent with the known role of the IL-1 cytokine family in implantation and pregnancy. Additionally, we confirm in a prospective investigation the positive relationship between detectable serum IL-1ß at the start of IVF cycle and outcome.

Blastocyst development rate influences implantation and live birth rates of similarly graded euploid blastocysts.

OBJECTIVE: To determine whether the blastocyst development rate, as assessed by the day of trophectoderm biopsy (day 5 vs. day 6), affects the live birth rate (LBR) of similarly graded euploid blastocysts. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): Patients who underwent frozen-thawed single euploid blastocyst transfers from 2013 to 2016 were included. Blastocyst morphologic grading was performed on day 5 or day 6 before the biopsy, with embryos designated into the following groups: good (3-6AA, 3-6AB, and 3-6BA), average (2-6BB), and poor (2-6BC and 2-6CB). INTERVENTION(S): Frozen-thawed embryo transfer. MAIN OUTCOME MEASURE(S): Implantation rate (IR) and LBR. RESULT(S): A total of 701 frozen-thawed single euploid blastocyst transfer cycles were included. Cycles in which day 5 blastocysts were transferred (n = 366) were associated with a significantly higher LBR than those in which day 6 blastocysts were transferred (n = 335; 60.4% vs. 44.8%). The odds ratio remained significant after controlling for all confounders, including the blastocyst grading. Furthermore, there was a significant difference in LBRs between good-quality, average-quality, and poor-quality blastocysts (67.8%, 53.4%, and 29.5%, respectively). Embryos reaching good-quality blastocysts on day 5 yielded significantly higher LBR (72.8% vs. 56.5%) and IR (77.7% vs. 58.7%) compared with those reaching similar quality blastocysts on day 6. Similarly, day 5 average-quality embryos conveyed a significantly higher IR compared with day 6 embryos of the same quality (64.4% vs. 53.4%). CONCLUSION(S): In addition to aneuploidy assessment, the speed of embryo development to the blastocyst stage and an evaluation of blastocyst morphology are critical to selecting the best embryo.

A 34-Week Size Uterus with a Complete Hydatidiform Mole: Hook Effect and Severe Anemia with No Vaginal Bleeding.

Complete hydatidiform mole is an abnormal pregnancy that usually presents with vaginal bleeding and markedly elevated serum ß-hCG levels. We report a rare case of complete hydatidiform mole occurring in a 16-year-old nulligravid who presented with a 34-week size uterus and a relatively low serum ß-hCG level (722 IU/L)-likely related to the "hook effect"-and severe anemia (hemoglobin: 6.1 g/dL) despite the absence of vaginal bleeding. She also reported right flank pain and was diagnosed with moderate right hydronephrosis owing to the compression exerted by the enlarged uterus on the right ureter. The patient received a total of 6 units of packed red blood cells and was managed by dilation and evacuation followed by serial monitoring of serum ß-hCG levels. Therefore, complete mole can present with symptoms related to an enlarged uterus and severe anemia before the occurrence of vaginal bleeding. It is also important to note that a negative urine pregnancy test or relatively low serum ß-hCG level should prompt repeating the measurement on diluted sample to prevent the "hook effect."

High serum IGF-1 levels are associated with pregnancy loss following frozen-thawed euploid embryo transfer cycles.

An elevated level of insulin growth factor (IGF-1) in rat uterine fluid has been shown to exert detrimental effects of embryo development possibly leading to an increase in pregnancy loss. Interestingly, the administration of somatostatin to rats undergoing superovulation reduced IGF-1 levels in uterine luminal fluid and thus reversed its deleterious effects on embryo development and increased the number of normal embryos. Therefore, we investigated whether serum levels of IGF-1 correlate with the incidence of pregnancy loss following IVF. To account for aneuploidy and the effect of hormonal supplementation on serum IGF levels, we only included natural frozen-thawed euploid embryo transfer (N-FET) cycles. Sera collected in the follicular phase (cycle day 10) were tested for levels of IGF-1, IGF-2, and IGF-binding protein 1 (IGFBP-1) using quantitative ELISA. A total of 156 N-FET cycles were included: 120 resulted in a live birth whereas 36 led to a first trimester pregnancy loss. Women with a pregnancy loss had significantly higher serum IGF-1 levels compared to those who achieved a live birth (18.0 ±â€¯1.1 vs. 14.6 ±â€¯0.7 ng/mL, respectively). The two groups had comparable serum IGF-2 and IGFBP-1 levels. There was no significant difference in maternal age, body mass index, gravidity, parity, number of prior miscarriages, peak endometrial thickness, or infertility diagnosis between the two groups. In conclusion, women undergoing euploid blastocyst transfer with elevated serum IGF-1 concentrations may be at increased risk of pregnancy loss. This may constitute a novel molecular explanation of pregnancy loss of euploid conceptus.

Optimizing the first-line fertility treatment.

The objective of this study was to identify sperm score thresholds to achieve satisfactory intrauterine insemination (IUI) success rates according to the response to stimulation with clomiphene citrate (CC). To minimize the confounding effect of female age, we included only CC/IUI cycles of women ≤35 years old. A total of 1,194 CC/IUI cycles were included. Semen volume, concentration, and motility influenced the clinical pregnancy rate (CPR). Normal morphology (≥4%) was associated with a comparable CPR with 3%, 2%, and 1% normal forms (15.6%, 16.1%, 18.1%, and 13.1%, respectively). A combination of the total number of motile spermatozoa in the ejaculate before semen preparation (TM) at a threshold ≥20 × 106 was associated with a CPR of 17.8% compared to 4.6% for a threshold <20 × 106 (p < .001). Interestingly, the TM threshold to achieve satisfactory outcomes was lower (10 × 106) in patients who had an optimal response to CC (≥2 dominant follicles with an endometrial thickness ≥7 mm) compared to 40 × 106 for those who had a suboptimal response (one dominant follicle with an endometrial thickness <7 mm). In conclusion, the response to superovulation with CC determines each patient's TM threshold required for satisfactory outcomes. Couples whose TM is below the threshold may benefit from a superovulation with gonadotropins or in vitro fertilization.

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.

One thousand seventy-eight autologous IVF cycles in women 45 years and older: the largest single-center cohort to date.

PURPOSE: The purpose of this study was to determine IVF outcomes in women 45 years and older using autologous oocytes. METHODS: This is a retrospective cohort study reviewing all IVF cycles in women ≥ 45 years old from January 1995 to June 2015 that were conducted at one academic medical center. One thousand seventy-eight fresh, autologous IVF cycles met inclusion criteria. PGD/S, natural IVF, and donor egg cycles were excluded. Outcomes were analyzed for the different age groups (age 45, n = 773; age 46, n = 221; age 47, n = 57; age 48, n = 22; age 49, n = 5). Primary outcome measures included IVF cycle characteristics, total pregnancy loss, clinical pregnancy, and live birth rates, and were stratified according to patient age. RESULTS: Mean age of patients in the study cohort was 45.4 ± 0.72. 11.7% of patients did not start due to an elevated FSH or cyst and 28.5% of patients were canceled prior to oocyte retrieval. The overall pregnancy rate per transfer was 18.7% (117/626), of which 82.1% ended in a pregnancy loss. The overall clinical pregnancy and live birth rates per transfer were 9.6 and 3.4%, respectively, which did not differ between age groups. Per cycle start women aged 45 had significantly higher positive pregnancy rates compared to women aged 46 and 47 (14.1 vs. 8.6 vs. 5.9%, p = 0.04). For women 45 years old, the live birth rate was 2.9% per cycle start and was 4.4% per embryo transfer. Of the 21 live births, 20 were in women aged 45 and one live birth was in a 46-year-old woman. There were no live births in any patient with ≤ 4 oocytes retrieved. CONCLUSION: Autologous IVF in women aged 45 with acceptable ovarian reserve is not futile; however, it does carry very low prognosis. Patients aged 46 and older should be counseled appropriately that a live birth seems highly unlikely.

Unilateral pleural effusion as the sole clinical presentation of severe ovarian hyperstimulation syndrome: a systematic review.

The pathophysiology of isolated pleural effusion in ovarian hyperstimulation syndrome (OHSS) is not well defined. The objective of the current review is to delineate the pathophysiology, risk factors, preventive measures, and therapeutic options of isolated pleural effusion in severe OHSS. Major databases were searched until June 2016. Studies evaluating women who presented with pleural effusion as the sole extra-ovarian manifestation of severe OHSS were included. Data were extracted from 24 articles encompassing 30 reported cases. Values were expressed as mean ± SEM. Patients were young (31.5 ± 0.8 years old) and 29.1% of them were diagnosed with polycystic ovary syndrome. All the patients received human chorionic gonadotropin to trigger oocyte maturation. Estradiol level was 3110 ± 330 pg/mL on the day of the ovulatory trigger. Dyspnea was the presenting symptom in 86.6% of the patients. Pleural effusion was predominantly on the right side (80%). Ninety percent of the patients underwent thoracentesis (4332 ± 769 mL): 66.7% exudate and 33.3% transudate. Fluid initially accumulates in the peritoneal cavity then enters the pleural space due to the pressure gradient through the thoracic duct and diaphragmatic defects, which are more common on the right side. The risk factors, prevention, and management, which are also discussed in this review, are similar to those of severe OHSS.

Assessment of embryo morphology and developmental dynamics by time-lapse microscopy: is there a relation to implantation and ploidy?

Time-lapse microscopy (TLM) is an exciting novel technology with great potential for enhancing embryo selection in the embryology laboratory. This non-invasive objective assessment of embryos has provided a new tool for predicting embryo development and implantation potential. TLM detects several morphological phenomena that are often missed with static observations using conventional incubators, such as irregular divisions, blastocyst collapse and re-expansion, timing of blastocoel appearance, and timing of formation and internalization of fragments. Nevertheless, it should be recognized that conventional morphological assessment has been widely accepted as the gold standard by most embryologists. TLM can enhance conventional morphological assessments to improve embryo selection and subsequent reproductive outcomes. Furthermore, morphokinetic parameters can aid in differentiating between euploid and aneuploid embryos, although they are not sufficiently accurate to replace preimplantation genetic testing for aneuploidy. Morphokinetic assessment together with chromosomal screening may ultimately help identify euploid embryos with the highest developmental potential.

Optimal parameters for determining the LH surge in natural cycle frozen-thawed embryo transfers.

BACKGROUND: There is no consensus on the exact parameters that define the LH surge for natural cycle frozen-thawed embryo transfers (NC-FET). Accurately determining the LH surge would affect the timing, and subsequently the success rates, of embryo transfer. Therefore, the aim of this study was to delineate the optimal levels and relationship for luteinizing hormone (LH) and estradiol in an effort to optimally identify the LH surge in NC-FET. METHODS: It is a retrospective study that was performed in an academic medical center. Patients who underwent blastocyst NC-FET who either had preimplantation genetic screening (PGS) or were <35 years old but did not undergo PGS (non-PGS) were included in separate analyses. They were divided into two groups: Group A included patients whose LH surge was defined as the first attainment of LH ≥ 17 IU/L during the follicular phase with a ≥30% drop in estradiol levels the following day; group B encompassed patients whose LH level continued to rise and the surge was defined as the highest serum LH level occurring a day after LH ≥ 17 IU/L despite a ≥ 30% drop in estradiol levels. The main outcomes measures were implantation and live birth rates. RESULTS: Four hundred-seven non-PGS and 284 PGS NC-FET were included. Among non-PGS cycles, group A was associated with significantly higher implantation rates (48.7% vs. 38.1%) and live birth rates (52.9% vs. 40.1%) compared to group B. In contrast, group A and B had comparable live birth rates among PGS cycles. CONCLUSIONS: Among non-PGS cycles, measuring LH and estradiol levels the day after an LH ≥ 17 IU/L and defining the surge as the first day of LH ≥ 17 IU/L in the context of a ≥ 30% drop in estradiol the following day was associated with better NC-FET outcomes than defining the surge as the day representing the highest serum LH level despite a ≥30% drop in estradiol levels.

Streptococcal toxic shock syndrome occurring in the third trimester of pregnancy: A case report.

Group A streptococcal (GAS) toxic shock syndrome (TSS) is a rare life-threatening illness. Most reported cases have occurred in the post-partum period. Here, we report a rare case of a primigravid who developed GAS TSS in the third trimester. We also review the potential preventive measures and treatment modalities for this syndrome. A 29-year-old primigravid presented at 36 weeks' gestation with diarrhea, abdominal pain, fever, and fetal bradycardia. She underwent an emergency cesarean section and was subsequently diagnosed with GAS TSS. She had a complicated post-partum course marked by a 3-month hospital stay and major sequelae. Her infant died on post-partum day 4. GAS TSS should be considered in the differential diagnosis of pregnant patients presenting with fever and rapid onset of septic shock. A consideration to treat GAS that is detected incidentally during routine screening for group B streptococcus is suggested.

Sliding scale HCG trigger yields equivalent pregnancy outcomes and reduces ovarian hyperstimulation syndrome: Analysis of 10,427 IVF-ICSI cycles.

OBJECTIVE: To evaluate pregnancy outcomes and the incidence of ovarian hyperstimulation syndrome (OHSS) using a sliding scale hCG protocol to trigger oocyte maturity and establish a threshold level of serum b-hCG associated with optimal oocyte maturity. DESIGN: Retrospective cohort. SETTING: Academic medical center. PATIENTS: Fresh IVF cycles from 9/2004-12/2011. INTERVENTION: 10,427 fresh IVF-ICSI cycles met inclusion criteria. hCG was administered according to E2 level at trigger: 10,000IU vs. 5,000IU vs. 4,000IU vs. 3,300IU vs. dual trigger (2mg leuprolide acetate + 1,500IU hCG). Serum absorption of hCG was assessed according to dose and BMI. MAIN OUTCOME MEASURES: Oocyte maturity was analyzed according to post-trigger serum b-hCG. Fertilization, clinical pregnancy, live birth and OHSS rates were examined by hCG trigger dose. RESULTS: Post-trigger serum b-hCG 20-30, 30-40, and 40-50 mIU/mL was associated with reduced oocyte maturity as compared b-hCG >50 (67.8% vs. 71.4% vs. 73.3% vs. 78.9%, respectively, P<0.05). b-hCG 20-50 mIU/mL was associated with a 40.1% reduction in live birth (OR 0.59, 95% CI 0.41-0.87). No differences in IVF outcomes per retrieval were seen for varying doses of hCG or dual trigger when controlling for patient age. The incidence of moderate to severe OHSS was 0.13% (n = 14) and severe OHSS was 0.03% (n = 4) of cycles. CONCLUSIONS: Moderate stimulation with sliding scale hCG at trigger and fresh transfer is associated with low rates of OHSS and favorable pregnancy rates. Doses as low as 3,300IU alone or dual trigger with 1,500IU are sufficient to facilitate oocyte maturity.

Vitamin D Decreases Serum VEGF Correlating with Clinical Improvement in Vitamin D-Deficient Women with PCOS: A Randomized Placebo-Controlled Trial.

Vascular endothelial growth factor (VEGF) has been suggested to play a role in the pathophysiology of polycystic ovary syndrome (PCOS) and may contribute to increased risk of ovarian hyperstimulation syndrome (OHSS) in affected individuals. Vitamin D (VitD) supplementation improves multiple clinical parameters in VitD-deficient women with PCOS and decreases VEGF levels in several other pathologic conditions. Unveiling the basic mechanisms underlying the beneficial effects of vitamin D on PCOS may enhance our understanding of the pathophysiology of this syndrome. It may also suggest a new treatment for PCOS that can improve it through the same mechanism as vitamin D and can be given regardless of vitamin D levels. Therefore, we aimed to explore the effect of VitD supplementation on serum VEGF levels and assess whether changes in VEGF correlate with an improvement in characteristic clinical abnormalities of PCOS. This is a randomized placebo-controlled trial conducted between October 2013 and March 2015. Sixty-eight VitD-deficient women with PCOS were recruited. Women received either 50,000 IU of oral VitD3 or placebo once weekly for 8 weeks. There was a significant decrease in serum VEGF levels (1106.4 ± 36.5 to 965.3 ± 42.7 pg·mL-1; p < 0.001) in the VitD group. Previously reported findings of this trial demonstrated a significant decrease in the intermenstrual intervals, Ferriman-Gallwey hirsutism score, and triglycerides following VitD supplementation. Interestingly, ∆VEGF was positively correlated with ∆triglycerides (R² = 0.22; p = 0.02) following VitD supplementation. In conclusion, VitD replacement significantly decreases serum VEGF levels correlating with a decrease in triglycerides in women with PCOS. This is a novel molecular explanation for the beneficial effects of VitD treatment. It also suggests the need to investigate a potential role of VitD treatment in reducing the incidence or severity of OHSS in VitD-deficient women with PCOS.

Unilateral Salpingectomy and Methotrexate Are Associated With a Similar Recurrence Rate of Ectopic Pregnancy in Patients Undergoing In Vitro Fertilization.

STUDY OBJECTIVE: To determine whether different treatment approaches of ectopic pregnancy (EP), particularly unilateral salpingectomy and methotrexate, affect its recurrence rate in patients undergoing in vitro fertilization (IVF). DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: An academic medical center. PATIENTS: Patients with a history of a previous EP who achieved pregnancy after IVF cycles between January 2004 and August 2015 were included. The recurrence rate of EP was compared between patients who underwent different treatment approaches for a previous EP. INTERVENTIONS: IVF. MEASUREMENTS AND MAIN RESULTS: A total of 594 patients were included. Seventeen patients had a recurrence of EP (2.9%). Patients with a history of ≥2 EPs were associated with a significantly higher recurrence rate of EP than those with 1 previous EP (8.5% vs. 1.8%; p = .01; odds ratio [OR] = 2.2; 95% confidence interval [CI], 1.2-4.4). Patients who underwent unilateral salpingectomy (n = 245) had a comparable recurrence rate of EP after IVF with those who received methotrexate (n = 283) (3.6% vs. 2.8%; p = .5; OR = 1.3; 95% CI, 0.4-3.4). This OR remained unchanged after adjusting for patient's age, number of previous EPs, number of transferred embryos, and peak estradiol level during stimulation (adjusted OR = 1.4; 95% CI, 0.5-3.8). None of the patients who underwent bilateral salpingectomy (n = 45) or salpingostomy (n = 21) had a recurrence of EP after IVF. CONCLUSION: The recurrence rate of EP significantly correlates with the number of previous EPs. Treatment of EP with methotrexate has a comparable recurrence rate of EP after IVF with unilateral salpingectomy. Therefore, the risk of recurrence should not be a reason to favor salpingectomy over methotrexate in this population.