Association between low fetal fraction and hypertensive disorders of pregnancy in in vitro fertilization-conceived pregnancies.

BACKGROUND: Fetal fraction from noninvasive prenatal screening has been used as a predictive marker for hypertensive disorders of pregnancy in spontaneous pregnancies. OBJECTIVE: We aimed to determine whether fetal fraction from noninvasive prenatal screening predicts hypertensive disorders of pregnancy in pregnancies conceived by assisted reproductive technology, stratified by fresh and frozen embryo transfer. STUDY DESIGN: Retrospective cohort study of women with singleton pregnancies who underwent fresh or frozen embryo transfer, had noninvasive prenatal screening, and had a live birth >20 weeks at a single institution from 2013 to 2019. Women with major anomalies, nonreportable noninvasive prenatal screening, or chronic hypertension were excluded. Fetal fraction was corrected for gestational age, noninvasive prenatal screening platform, and defined as low if it is less than fifth percentile for the study population. The primary outcome was hypertensive disorders of pregnancy during delivery hospitalization, stratified by fresh vs frozen embryo transfer. We performed multivariable logistic regression analyses to determine whether low fetal fraction predicts hypertensive disorders of pregnancy for fresh and frozen embryo transfer, controlling for age, prepregnancy body mass index, heparin use, low-dose aspirin use, estradiol level if fresh embryo transfer, and trophectoderm biopsy and cycle type if frozen embryo transfer. RESULTS: We included 81 women with low fetal fraction and 847 women with normal fetal fraction. The adjusted prevalence of hypertensive disorders of pregnancy in women with low fetal fraction was 24.9% in fresh embryo transfer and 34.5% in frozen embryo transfer. In fresh embryo transfer pregnancies, the odds of hypertensive disorders of pregnancy were higher among women with low fetal fraction (adjusted odds ratio, 2.46; 95% confidence interval, 1.07-5.30; P=.026). In frozen embryo transfer pregnancies, there was no association between low fetal fraction and hypertensive disorders of pregnancy (adjusted odds ratio, 1.43; 95% confidence interval, 0.69-2.88; P=.321). CONCLUSION: Low fetal fraction is associated with hypertensive disorders of pregnancy in women who conceive by fresh embryo transfer. Fetal fraction may represent a clinically useful marker for screening for hypertension and allow clinicians to target risk reduction strategies, such as low-dose aspirin, in pregnancies conceived by fresh embryo transfer.

Clinical implications of telemedicine for providers and patients.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in paradigm shifts in the delivery of health care. Lockdowns, quarantines, and local mandates forced many physician practices around the United States to move to remote patient visits and adoption of telemedicine. This has several long-term implications in the future practice of medicine. In this review we outline different models of integrating telemedicine into both male and female fertility practices and recommendations on performing video physical examinations. Moving forward we foresee two general models of integration: one conservative, where initial intake and follow-up is performed remotely, and a second model where most visits are performed via video and patients are only seen preoperatively if necessary. We also discuss the impact THAT telemedicine has on coding and billing and our experience with patient satisfaction.

Body mass index is not associated with donor oocyte recipient success: an ideal study using a paired analysis of sibling-oocytes.

OBJECTIVE: To determine whether a higher body mass index (BMI) adversely affects endometrial receptivity. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: All donor egg recipients (DERs) who received fresh sibling-oocytes (oocytes from a donor that were retrieved from a single controlled ovarian hyperstimulation [COH] cycle and split between two recipients) at our center over a 7-year period were included. INTERVENTIONS: COH of a donor with fresh embryo transfer to recipients of differing BMI. The two recipients of the sibling-oocytes were paired and categorized based on BMI: group A (normal weight, BMI 18.5-24.9 kg/m2) and group B (overweight/obese, BMI >25.0 kg/m2). MAIN OUTCOME MEASURES: The primary outcome was implantation rate. Secondary outcomes were positive pregnancy rate and live birth rate. RESULTS: A total of 408 patients had received oocytes from a split donor oocyte cycle. There were 71 pairs of patients (142 recipients) that had discrepant BMI categories and were analyzed. Implantation rates were similar for the two groups (54.5%±5.3% vs. 56.3%±4.8% for group A and B, respectively, P=0.72). The positive pregnancy rate (77.5% vs. 80.3%, P=0.28) and live birth rate (54.9% vs. 60.6%, P=0.33) for groups A and B were also found to be similar. CONCLUSIONS: In this idealized model that controls to the greatest degree possible for factors that would impact implantation, we found that a higher BMI did not reduce implantation, positive pregnancy, or delivery rates. These findings suggest that a higher BMI does not adversely affect uterine receptivity.

Oocyte donation: insights gleaned and future challenges.

With the first successful report of an IVF pregnancy achieved via donor oocytes in 1984, the applications of assisted reproductive technology (ART) were further expanded to include women unable to conceive with their own oocytes. Today, oocyte donation makes up an increasingly large percentage of all ART cycles worldwide. Oocyte donation presents several unique challenges to clinicians as two separate interests, those of the donor and those of the recipient, must be represented. These challenges include successful preparation of the endometrium in donor oocyte recipients, the synchronization of donor/recipient cycles, and the optimization of ovarian stimulation while maximizing donor safety. Facing these challenges has not only allowed for the creation of successful donor egg programs but has also provided insights into many aspects of ART. Much of what we know about the window of implantation, frozen ET procedures, triggering of oocyte maturation, and fertility preservation has been learned through experience and investigations with donor egg cycles. Not only has oocyte donation, through its optimization and wide use, provided new treatment opportunities for patients, it has also become a critical scientific tool to study many aspects of menstrual cycle dynamics and implantation. Concomitantly, with its increased efficiency, it has also raised several clinical and ethical challenges.

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.

Replacing single frozen-thawed euploid embryos in a natural cycle in ovulatory women may increase live birth rates compared to medicated cycles in anovulatory women.

PURPOSE: The goal of this study was to compare pregnancy outcomes between natural frozen embryo transfer (FET) cycles in ovulatory women and programmed FET cycles in anovulatory women after undergoing in vitro fertilization with preimplantation genetic screening (IVF-PGS). METHODS: This was a retrospective cohort study performed at an academic medical center. Patients undergoing single FET IVF-PGS cycles between October 2011 and December 2014 were included. Patients were stratified by type of endometrial replacement: programmed cycles with estrogen/progesterone replacement and natural cycles. IVF-PGS with 24-chromosome screening was performed on all included patients. Those patients with euploid embryos had single embryo transfer in a subsequent FET. The primary study outcome was live birth/ongoing pregnancy rate. Secondary outcomes included implantation, biochemical pregnancy, and miscarriage rates. RESULTS: One hundred thirteen cycles met inclusion criteria: 65 natural cycles and 48 programmed cycles. The programmed FET group was younger (35.9 ± 4.5 vs. 37.5 ± 3.7, P = 0.03) and had a higher AMH (3.95 ± 4.2 vs. 2.37 ± 2.4, P = 0.045). The groups were similar for BMI, gravidity, parity, history of uterine surgery, and incidence of Asherman's syndrome. There was also no difference in embryo grade at biopsy or transfer, and proportion of day 5 and day 6 transfers. Implantation rates were higher in the natural FET group (0.66 ± 0.48 vs. 0.44 ± 0.50, P = 0.02). There was no difference in the rates of biochemical pregnancy or miscarriage. After controlling for age, live birth/ongoing pregnancy rate was higher in natural FETs with an adjusted odds ratio of 2.68 (95% CI 1.22-5.87). CONCLUSIONS: Natural FET in ovulatory women after IVF-PGS is associated with increased implantation and live birth rates compared to programmed FET in anovulatory women. Further investigation is needed to determine whether these findings hold true in other patient cohorts.

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.

Morphologic grading of euploid blastocysts influences implantation and ongoing pregnancy rates.

OBJECTIVE: To determine whether blastocyst grading can predict pregnancy outcomes in the frozen-thawed embryo transfer (FET) of euploid blastocysts. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): Women who underwent FET of euploid embryo(s) between January 2013 and December 2015, with blastocysts were divided into four groups based on their morphologic grading before cryopreservation: excellent (≥3AA), good (3-6AB, 3-6BA, 1-2AA), average (3-6BB, 3-6AC, 3-6CA, 1-2AB, 1-2BA), and poor (1-6BC, 1-6CB, 1-6CC, 1-2BB). INTERVENTION(S): FET. MAIN OUTCOMES MEASURE(S): Ongoing pregnancy rate (OPR). RESULT(S): A total of 417 FET cycles (477 embryos) were included. Excellent-quality embryos (n = 38) yielded a statistically significantly higher OPR than poor-quality embryos (n = 106) (84.2% vs. 35.8%; adjusted odds ratio 11.0; 95% confidence interval, 3.8-32.1) and average-quality embryos (n = 197) (84.2% vs. 55.8%; adjusted odds ratio 4.8; 95% confidence interval, 1.7-13.3). Good-quality embryos (n = 76) were associated with a statistically significantly higher OPR than poor-quality embryos (61.8% vs. 35.8%). These odds ratios were adjusted for patient's age, body mass index, number of transferred embryos, type of frozen cycle, peak endometrial thickness, day of trophectoderm biopsy (5 or 6), and total number of euploid embryos for each patient. An inner cell mass grade of A yielded a statistically significantly higher OPR than ICM grade C (76.2% vs. 13.5%) or grade B (76.2% vs. 53.6%) after controlling for all confounders. CONCLUSION(S): Contrary to prior published studies, the current data suggest that blastocyst morphologic grading and particularly inner cell mass grade is a useful predictor of OPR per euploid embryo. Morphologic grading should be used to help in the selection among euploid blastocysts.

Spontaneous bilateral torsion of fallopian tubes presenting as primary infertility.

UNLABELLED: Case presented at "Stump the Professors" 44th American Association of Gynecologic Laparoscopists Global Congress on Minimally Invasive Gynecology, NV, USA, 15-19 November 2015 BACKGROUND: Spontaneous torsion of the fallopian tubes is a rare condition, usually seen in acute settings or as incidental findings during laparoscopy. PRESENTATION OF THE CASE: A 34-year-old nulligravid woman with inability to conceive for 7 months presented to our center. Her hysterosalpingography revealed a blind-ending right fallopian tube, and a blocked and dilated left fallopian tube. Laparoscopy showed a long, auto-amputated right fallopian tube, disconnected from the fimbriae and a long, dilated left fallopian tube, with several twists around its axis. Bilateral salpingectomy was performed. The patient subsequently underwent IVF, resulting in an ongoing pregnancy. CONCLUSION: Spontaneous torsion of the fallopian tubes can manifest as primary infertility without any antecedent symptoms, and should be considered in the differential diagnosis of bilateral tubal obstruction.

Preimplantation genetic screening: who benefits?

OBJECTIVE: To compare IVF outcomes between women undergoing frozen transfers of blastocysts verified as euploid by preimplantation genetic screening (PGS) with patients undergoing fresh nonbiopsied blastocyst transfers. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): All patients undergoing IVF-PGS cycles between January 2010 and November 2014 were included (n = 274). Patients were compared with a control group consisting of all fresh blastocyst transfers that occurred during the same period (n = 863). INTERVENTION(S): Patients underwent IVF-PGS with 24-chromosome screening. Patients with euploid embryos had transfer of one to two embryos in a subsequent frozen ET cycle. MAIN OUTCOME MEASURE(S): Implantation, clinical intrauterine gestation (CIG), miscarriage, biochemical pregnancy (BC), and live birth (LB) rates were compared. RESULT(S): Odds ratios (ORs) were estimated for outcomes in women undergoing PGS versus controls. Among patients ≤37 years old, there were no differences in CIG and LB rates for single (adjusted ORs [aORs], 1.20 [95 %confidence interval {CI}, 0.66-2.21]; 1.21 [95% CI, 0.66-2.2]) and double ETs (aORs, 1.09 [95% CI, 0.54-2.18]; 0.87 [95% CI, 0.44-1.7]). BC and miscarriage rates were also similar. For patients >37 years old, CIG and LB rates were increased for single (aORs, 3.86 [95% CI, 1.25-11.9]; 8.2 [95% CI, 2.28-29.5]) and double ETs (aORs, 9.91 [95% CI, 2.0-49.6]; 8.67 [95% CI, 2.08-36.2]) with no difference in BC and miscarriage rates. A per-retrieval analysis of the >37 group failed to demonstrate any difference in CIG or LB rates. CONCLUSION(S): Among patients ≤37, IVF-PGS does not improve CIG, LB, and miscarriage rates. IVF-PGS in women >37 improved CIG and LB rates. However, per cycle, the PGS advantage in this age group does not persist.

How low is too low? Cycle day 28 estradiol levels and pregnancy outcomes.

OBJECTIVE: To determine the utility of cycle day 28 estradiol (E2) levels in predicting pregnancy outcomes after IVF. DESIGN: Retrospective, cohort study. SETTING: Academic medical center. PATIENT(S): All IVF cycles resulting in a positive pregnancy test result at our center between January 2007 and December 2012 were included. INTERVENTION(S): In vitro fertilization with fresh embryo transfer. MAIN OUTCOME MEASURE(S): A total of 5,471 IVF cycles were identified. Cycles were stratified by day-28 E2 level (pg/mL) into three groups: A: ≤50; B: 51-100; and C: >100. Outcomes measured were live birth, clinical pregnancy, biochemical, ectopic, and spontaneous abortion rates. RESULT(S): There were 806, 588, and 4,077 IVF pregnancies in groups A, B, and C, respectively. Live birth rates were lower in groups A (15.4%) and B (41.2%) compared with group C (77.4%), representing decreased odds of live birth in patients with E2 levels of ≤50 pg/mL (odd ratio 0.05, 95% confidence interval 0.04-0.07) and in patients with levels of 51-100 pg/mL (odds ratio 0.20, 95% confidence interval 0.17-0.25) compared with patients with levels >100 pg/mL. Rates of biochemical and ectopic pregnancies were higher in groups A (66.5%, 6.20%) and B (30.7%, 3.57%) compared with group C (7.31%, 0.66%). An hCG level <50 mIU/mL was associated with increased odds of a biochemical pregnancy and decreased odds of a live birth. CONCLUSION(S): Low E2 levels early in IVF pregnancies are associated with poorer pregnancy outcomes. Estradiol can be used alone or in conjunction with hCG levels to predict the odds of a live birth.

Autologous endometrial coculture biopsy: is timing everything?

OBJECTIVE: To determine whether endometrial biopsy timing affects implantation rates and pregnancy outcomes in patients undergoing in vitro fertilization (IVF) with autologous endometrial coculture (AECC). DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): All patients with a history of at least one failed IVF cycle who underwent an IVF-AECC cycle at our center from May 2004 to November 2013 were included. INTERVENTION(S): Patients underwent luteal-phase endometrial biopsy in preparation for IVF. Biopsy samples were used for IVF in either the subsequent menstrual cycle or a future cycle. Embryos were cultured in AECC media and transferred on day 3. MAIN OUTCOME MEASURE(S): A total of 2,533 cycles of 1,719 patients who underwent an IVF-AECC cycle were identified. Cycles were stratified by endometrial biopsy timing. Clinical outcomes, including implantation, pregnancy, and live birth rates, were analyzed and compared between the two groups. RESULT(S): A total of 1,416 coculture biopsies were performed in the menstrual cycle before IVF and 1,117 were performed more than one cycle before IVF. The two groups were similar in age, body mass index, number of mature oocytes retrieved, and best embryo grade. There were no significant differences in implantation, clinical pregnancy, or live birth rates, with adjusted relative risks of 1.02 (95% confidence interval [CI] 0.92-1.13), 1.02 (95% CI 0.91-1.14), and 0.99 (95% CI 0.86-1.16), respectively. CONCLUSION(S): Coculture biopsy in the cycle preceding IVF does not increase implantation, clinical pregnancy, or live birth rates compared with biopsies performed more than one cycle before IVF. Previously demonstrated improvements in embryo quality and pregnancy outcomes in patients undergoing IVF with AECC are probably not attributable to biopsy-induced endometrial injury.

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.