Pregnancy rates after pre-implantation genetic screening for aneuploidy are only superior when trophectoderm biopsy is performed on hatching embryos.

PURPOSE: In vitro fertilization with trophectoderm embryo biopsy and pre-implantation genetic screening with comprehensive chromosomal screening (PGS-CCS) for aneuploidy is becoming increasingly more popular. Embryos are cryopreserved and implanted in a subsequent frozen thawed embryo transfer cycle (FET). No studies have investigated differences in pregnancy outcomes by timing of trophectoderm biopsy relative to stages of blastocyst development. METHODS: Retrospective study of all patients (n = 363) at a single IVF center between January 1, 2013 and December 31, 2016 undergoing single embryo transfer with PGS-CCS where embryos were cryopreserved with subsequent FET. Embryo expansion and grading was assessed both at the time of biopsy and transfer. Pregnancy rates were analyzed by embryo expansion and embryo grading. RESULTS: Implantation, clinical pregnancy, and live birth rates improved significantly with increased embryo expansion at the time of embryo biopsy (P < 0.001). Pregnancy loss decreased with increases in embryo expansion prior to biopsy (P < 0.001). Superior live birth rates with PGS-CCS were seen when embryos were hatching at the time of biopsy (p < 0.001). For fresh and frozen embryo transfers without PGS-CCS, embryo expansion did not affect pregnancy outcomes. CONCLUSIONS: PGS-CCS significantly increases implantation and live birth rates only if embryos are hatching at the time of biopsy. The embryo biopsy itself on a non-hatching embryo significantly damages the embryo in ways which are not reflected in future embryo expansion. IVF labs should wait until embryos hatch before performing trophectoderm biopsy.

Use of Concomitant FSH with hCG at the Time of Trigger May Improve Success Rates of Couples with Poor Ovarian Response Undergoing Gonadotropin Therapy with IUI.

OBJECTIVE: To investigate if administration of an additional dose of gonadotropins concomitantly to human chorionic gonadotropin (hCG) trigger increases pregnancy rates in patients undergoing intrauterine insemination (IUI) with controlled ovarian hyperstimulation (COH). STUDY DESIGN: This is a retrospective cohort study of all gonadotropin-IUI cycles performed by a single physician in a private practice between January 2012 and September 2013. Control cycles were those in which follicle-stimulating hormone (FSH) was discontinued prior to the day of hCG trigger shot, and study cycles received continuous FSH including the day of hCG trigger shot. A total of 423 cycles from 239 patients were included; 275 (65.5%) were control cycles (137 patients), and 146 (34.7%) were study cycles (102 patients). RESULTS: Pregnancy rates were comparable in both control and study groups (15.27% vs. 15.07%, respectively, p=0.956). There was a 42% increase in multiple gestations in the study group; however, the difference was not statistically significant (p=0.155). Upon multivariate logistic regression, male factor infertility was the only variable that was associated with pregnancy outcomes. CONCLUSION: Continuous administration of FSH including the day of hCG trigger in patients undergoing COH with IUI does not seem to increase pregnancy rates. Our suggested protocol might be beneficial in patients with poor ovarian response.

Initial maternal serum human chorionic gonadotropin levels in pregnancies achieved after assisted reproductive technology are higher after preimplantation genetic screening and after frozen embryo transfer: a retrospective cohort.

PURPOSE: Few published articles have compared initial hCG values across all different types of ART cycles, including cycles with fresh or frozen embryo transfer. No articles have compared initial hCG values in cycles utilizing preimplantation genetic screening (PGS). The purpose of this study is to compare initial hCG values after fresh embryo transfer, frozen embryo transfer, and after PGS. METHODS: This was a single-center retrospective cohort study at an academically affiliated private IVF center. All fresh and frozen embryo transfers between January 2013 and December 31, 2015 were included. We compared mean initial serum hCG values 14 days after oocyte retrieval for fresh cycles and 9 days after frozen embryo transfer. We examined cycles of single embryo transfer (SET) and double embryo transfer (DET). RESULTS: Two hundred elven IVF (fresh embryo transfer), 128 FET (frozen embryo transfer cycles, no PGS), and 111 PGS cycles (ovarian stimulation with embryo cryopreservation, PGS, and frozen transfer in a subsequent estrogen-primed cycle) with initial positive hCG values were analyzed. In patients achieving a positive hCG after SET, initial hCG values were higher after PGS compared to FET (182.4 versus 124.0 mIU/mL, p = 0.02) and IVF (182.4 versus 87.1 mIU/mL, p < 0.001) as well as FET compared to IVF (124.0 versus 87.1 mIU/mL, p < 0.01). After DET, initial hCG values were higher after PGS (222.8 mIU/mL) compared to FET (182.1 mIU/mL, p = 0.02) and IVF (131.1 mIU/mL, p = 0.001). CONCLUSIONS: Our study suggests that initial serum hCG values are higher after using PGS and higher after the transfer of a frozen embryo compared to a fresh embryo. This suggests that initial hCG values relate to the chromosomal status of embryos. Initial hCG values may help determine intervention and monitoring later in pregnancy.

The presence of multiple gestational sacs confers a higher live birth rate in women with infertility who achieve a positive pregnancy test after fresh and frozen embryo transfer: a retrospective local cohort.

BACKGROUND: After spontaneous conception, the rate of miscarriage is more common in multiple rather than singleton pregnancies. However, the incidence of miscarriage is lower in in-vitro fertilization twin versus singleton pregnancies. Most patients have little understanding of pregnancy outcomes once they achieve a positive pregnancy test. This study investigated the relationship between multiple pregnancy and miscarriage in women with infertility after fresh and frozen embryo transfer. METHODS: Retrospective local cohort study of all consecutive patients undergoing in-vitro fertilization at our institution (n = 1130), fresh or frozen embryo transfer, between January 1, 2008 and December 31, 2012. Patient characteristics (age, body mass index, initial hCG, maximum follicle stimulating hormone levels) and in-vitro fertilization parameters (estradiol levels, eggs retrieved, and endometrial thickness) were collected and statistically analyzed using T-test and Chi-square test (Stata version 10). Linear and logistic regression were used when appropriate. RESULTS: Overall, live birth rate for all cycles was 30.44% and total pregnancy loss was 6.55% - similar for fresh and frozen cycles despite a higher rate of biochemical pregnancies for frozen cycles. Among all pregnant patients, 62.48% had a live birth. Although clinical pregnancy rate was higher for fresh cycles, live birth rates were similar. In pregnancies where multiple sacs were demonstrated on ultrasound, live birth rates were higher despite 31% of patients losing at least one sac. This finding was comparable between fresh and frozen cycles. However, in patients under age 35 and using donor egg, no live birth advantage was seen in patients with multiple sacs. In fact, transferring more than one embryo did not increase live birth rate either. CONCLUSIONS: Despite the many maternal and fetal risks of multiple pregnancies, patients who achieve a positive pregnancy test with fresh and frozen in-vitro fertilization and who have more than one pregnancy sac are more likely ultimately to deliver at least one baby. This finding is true of both fresh and frozen embryo transfer cycles. This pregnancy advantage is not seen in young patients and in patients using donor egg, and single embryo transfer maximizes birth outcomes.

Endometrial thickness, Caucasian ethnicity, and age predict clinical pregnancy following fresh blastocyst embryo transfer: a retrospective cohort.

BACKGROUND: In-vitro fertilization (IVF) with blastocyst as opposed to cleavage stage embryos has been advocated to improve success rates. Limited information exists on which to predict which patients undergoing blastocyst embryo transfer (BET) will achieve pregnancy. This study's objective was to evaluate the predictive value of patient and cycle characteristics for clinical pregnancy following fresh BET. METHODS: This was a retrospective cohort study from 2003-2007 at an academic assisted reproductive program. 114 women with infertility underwent fresh IVF with embryo transfer. We studied patients undergoing transfer of embryos at the blastocyst stage of development. Our main outcome of interest was clinical pregnancy. Clinical pregnancy and its associations with patient characteristics (age, body mass index, FSH, ethnicity) and cycle parameters (thickness of endometrial stripe, number eggs, available cleaving embryos, number blastocysts available, transferred, and cryopreserved, and embryo quality) were examined using Student's T test and Mann-Whitney-U tests as appropriate. Multivariable logistic regression models were created to determine independent predictors of CP following BET. Receiver Operating Characteristic analyses were used to determine the optimal thickness of endometrial stripe for predicting clinical pregnancy. RESULTS: Patients achieving clinical pregnancy demonstrated a thicker endometrial stripe and were younger preceding embryo transfer. On multivariable logistic regression analyses, Caucasian ethnicity (OR 2.641, 95% CI 1.054-6.617), thickness of endometrial stripe, (OR 1.185, 95% CI 1.006-1.396) and age (OR 0.879, 95% CI 0.789-0.980) predicted clinical pregnancy. By receiver operating characteristic analysis, endometrial stripe >or= 9.4 mm demonstrated a sensitivity of 83% for predicting clinical pregnancy following BET. CONCLUSION: In a cohort of patients undergoing fresh BET, thicker endometrial stripe, Caucasian ethnicity, and younger age are positive predictors of clinical pregnancy after fresh BET. These findings may be useful in clinical management of infertile patients undergoing fresh BET cycles.

Impact of vitamin D3 dietary supplement matrix on clinical response.

CONTEXT: As a result of research suggesting increased health risk with low serum 25-hydroxycholecalciferol (25(OH)D), health care providers are measuring it frequently. Providers and patients are faced with treatment choices when low status is identified. OBJECTIVE: To compare the safety and efficacy of three vitamin D3 dietary supplements with different delivery matrices. SETTING AND DESIGN: A 12-week, parallel group, single-masked, clinical trial was conducted in Seattle, Washington and Kailua Kona, Hawaii. Sixty-six healthy adults with (25(OH)D) <33 ng/mL were randomly assigned to take one of three D3 supplements, ie, a chewable tablet (TAB), an oil-emulsified drop (DROP), or an encapsulated powder (CAP) at a label-claimed dose of 10,000 IU/day. Actual D3 content was assessed by a third party and the results adjusted based on the actual D3 content administered. Mean change in 25(OH)D/mcg D3 administered; difference in the proportion of D3 insufficient participants (ie, 25(OH)D ≤30 ng/mL) reaching sufficiency (ie, 25(OH)D ≥30 ng/mL); and mean change in serum 1, 25-dihydroxycholecalciferol were measured. RESULTS: In two of the three products tested, the measured vitamin D3 content varied considerably from the label-claimed dose. Differences in 25(OH)D/mcg D3 administered were significantly different between groups (P = .04; n = 55). Pairwise comparisons demonstrated DROP resulted in a greater increase than TAB (P < .05) but not than CAP. TAB was not different from CAP. The proportions reaching sufficiency were: 100% (TAB and CAP) and 80% (DROP) (P = .03 between groups; n = 55). 1, 25-Dihydroxycholecalciferol did not change significantly in any group. CONCLUSIONS: Oil-emulsified vitamin D3 supplements resulted in a greater mean change in serum 25(OH)D concentration, but fewer patients reaching vitamin D sufficiency, than chewable or encapsulated supplements.

Defining the role of bariatric surgery in polycystic ovarian syndrome patients.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women. To meet PCOS criteria, women must have a combination of hyperandrogenism, anovulation and ultrasound findings. Almost 10% of all reproductive age women worldwide show signs of PCOS. Although women often seek care for gynecological or body image concerns, many PCOS women are at risk for metabolic syndrome (MS). Many of the metabolic consequences are overlooked and undertreated by physicians because these patients tend to be young, reproductive age women. MS and obesity coexist commonly with PCOS. These young women are predisposed to glucose abnormalities and ultimately diabetes mellitus, dyslipidemia and eventually cardiovascular disease. Bariatric surgery can be an effective means of weight loss in PCOS women. Surgical techniques have become safer and less invasive over time and have been found to be effective in achieving significant weight loss. Surgical options have also increased, giving patients more choices. Bariatric surgery may prevent or reverse metabolic syndrome. Bariatric surgery may also have reproductive benefits in PCOS patients. Although bariatric surgery has historically been performed in older, reproductive aged women, it has recently gained favor in adolescents as well. This is of particular importance due to the prevalence of both PCOS and MS in adolescents. Treatment of PCOS and MS certainly requires a combination of medical therapy, psychological support and lifestyle modifications. These treatments are difficult and often frustrating for patients and physicians. Bariatric surgery can be effective in achieving significant weight loss, restoration of the hypothalamic pituitary axis, reduction of cardiovascular risk and even in improving pregnancy outcomes. Ultimately, bariatric surgery should be considered part of the treatment in PCOS women, especially in those with MS.

The "muffin test"--an alternative to the oral glucose tolerance test for detecting impaired glucose tolerance.

OBJECTIVE: The aim of this study was to compare the effectiveness of the "muffin test" (MT) with that of the oral glucose tolerance test (OGTT) in diagnosing impaired glucose tolerance (IGT). METHODS: This is a cross-sectional study in a single academic institution. The participants were 73 women aged 42 to 58 years, less than 36 months after menopause, recruited for the Kronos Early Estrogen Prevention Study Trial. After a 10-hour fasting blood draw, the participants were provided a muffin and a beverage. Two-hour glucose levels were assessed. A subset underwent metabolic testing consisting of an OGTT (n = 12) and a mixed-meal tolerance test (n = 10). The main outcome measures were the prevalence of IGT and 2-hour glucose measurements after each testing method. RESULTS: Two-hour glucose levels were linearly related to fasting values by multivariable linear regression. This association was exaggerated in overweight (body mass index, 25 kg/m2) women (coefficient, 1.43; P < 0.001). Two-hour OGTT and MT glucose levels were comparable (P > 0.05); 2-hour glucose levels after OGTT were slightly lower than after the mixed-meal tolerance test (P < 0.05). CONCLUSIONS: The prevalence of IGT was 11% (8 of 73). Fasting plasma glucose alone would have missed 63% of cases (five of eight cases). The MT demonstrated 100% sensitivity and specificity for diagnosing IGT compared with the gold standard OGTT. This small pilot study should be confirmed in a larger prospective group of participants.

Assessing and treating insulin resistance in women with polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is a highly prevalent hormonal and metabolic disorder among reproductive aged women worldwide. Women with PCOS have widely varying phenotypes and seek medical care for differing reasons. In addition to concern for menstrual cycle function, ovulation, hirsutism and acne, many PCOS women have abnormal glucose metabolism. While diabetes mellitus and impaired glucose tolerance are easily diagnosed, the diagnosis of and concern for insulin resistance as a precursor disorder is underappreciated. Insulin resistance may be the first important marker of metabolic disease in PCOS women at risk for metabolic syndrome and coronary artery disease.

Reproductive aging and its consequences for general health.

Reproductive aging coincides with endocrine changes that are not solely reproductive in nature and culminates in hypergonadotropic hypogonadism and amenorrhea. These changes are identifiable biochemically regardless of clinical manifestations. Changes in the hypothalamic-pituitary-ovarian axis are associated with changes in other hormonal axes, specifically the adrenal androgen and the somatotropic axis. A large body of literature indicates that reproductive aging is associated with a decline in the somatotropic axis. The interactions between reproductive aging and changes in the adrenal androgen axis are more complex and complicated by age-related declines in the adrenal axis early in the reproductive years. These changes may play an important role in overall health maintenance. Attempts to ameliorate hormonal declines with exogenous hormonal therapy have produced mixed results. Finally, the age-specific timing as well as the rapidity of the changes that occur with reproductive aging seems to have important consequences on metabolism, cardiovascular risk, cognition, bone density, and even mortality.

Mucocele of the appendix causing tubal factor infertility.

OBJECTIVE: To report on the safety of conservative management of a young woman with pseudomyxoma peritonei of appendiceal origin desiring fertility preservation. DESIGN: Case report. SETTING: IVF Center at Tertiary Hospital. PATIENT(S): A 32-year-old woman with primary infertility. INTERVENTION(S): Appendectomy, conservative second-look laparoscopy, and IVF. MAIN OUTCOME MEASURE(S): Persistence of active mucinous lesions in the peritoneal cavity, presence of abnormalities at colonoscopy, and maternal/fetal complications from IVF. RESULT(S): Normal second-look laparoscopy, no evidence of persistent disease, and successful intrauterine twin pregnancy following IVF. CONCLUSION(S): Pseudomyxoma peritonei of appendiceal origin is rare in young female patients. Although traditional therapy in older patients often involves aggressive surgical therapy, this case report demonstrates that patients desiring fertility can be managed conservatively and safely and still maintain successful pregnancy.