High estradiol levels in fresh embryo transfer cycles are not associated with detrimental impact on birth outcomes.

PURPOSE: There is an unclear relationship between estradiol levels and fresh embryo transfer (ET) outcomes. We determined the relationship between estradiol on the day of trigger, in fresh ET cycles without premature progesterone elevation, and good birth outcomes (GBO). METHODS: We identified autologous fresh ET cycles from 2015 to 2021 at multiple clinics in the USA. Patients with recurrent pregnancy loss, uterine factor, and elevated progesterone on the day of trigger (progesterone > 2 ng/mL or 3-day area under the curve > 4.5 ng/mL) were excluded. The primary outcome was GBO (singleton, term, live birth with appropriate weight). Log-binomial generalized estimating equations determined the likelihood of outcomes. RESULTS: Of 17,608 fresh ET cycles, 5025 (29%) yielded GBO. Cycles with estradiol ≥ 4000 pg/mL had a greater likelihood of GBO compared to cycles < 1000 pg/mL (aRR = 1.32, 95% CI 1.13-1.54). Pairwise comparisons of estradiol between < 1000 pg/mL versus 1000-1999 pg/mL and 1000-1999 pg/mL versus 2000-2999 pg/mL revealed a higher likelihood of GBO with higher estradiol (aRR 0.83, 95% CI 0.73-0.95; aRR 0.91, 95% CI 0.85-0.97, respectively). Comparisons amongst more elevated estradiol levels revealed that the likelihood of GBO remained similar between groups (2000-2999 pg/mL versus 3000-3999 pg/mL, aRR 1.04, 95% CI 0.97-1.11; 3000-3999 pg/mL versus ≥ 4000 pg/mL, aRR 0.96, 95% CI 0.9-1.04). CONCLUSION: In fresh ET cycles, higher estradiol levels were associated with an increased prevalence of GBO until estradiol 2000-2999 pg/mL, thereafter plateauing. In fresh ET candidates, elevated estradiol levels should not preclude eligibility though premature progesterone rise, and risk of ovarian hyperstimulation syndrome must still be considered.

Patient perspectives of telehealth for fertility care: a national survey.

PURPOSE: To evaluate patient satisfaction using telehealth for fertility care. METHODS: Cross-sectional survey using the validated telehealth usability questionnaire (TUQ) distributed nationally via fertility advocacy groups of fertility patients aged ≥ 18 years with self-reported use of telehealth for care. Patient satisfaction of telehealth for fertility care as determined by the TUQ questionnaire. The survey also included questions about telehealth related to usefulness, ease of use, effectiveness, reliability, and the option for patients to add open-ended comments related to their experiences using telehealth for fertility care. RESULTS: A total of 81 fertility patients completed the survey. Patients reported high rates of satisfaction (81.4%) with telehealth in areas of usefulness, ease of use, effectiveness, reliability, and satisfaction. However, many patients (60.5%) expressed a preference for in-person visits for their initial visit while the acceptability of telehealth increased for follow-up visits. Negative themes from respondent comments address that telehealth visits felt more impersonal and rushed. CONCLUSION: Fertility patients reported high satisfaction using telehealth for care. Patients still preferred in-person visits for initial consultations. For follow-up visits, most respondents favored telehealth or had no preference. Incorporation of telehealth in fertility practices should continue though it may be helpful for patients to be given options for visit types.

Ovarian stimulation for fertility preservation in an oncology patient with etonogestrel implant in place.

PURPOSE: To describe a case of a young woman who presented for fertility preservation and underwent ovarian stimulation with an etonogestrel implant in place. METHODS: A 24-year old, gravida 0, with an etonogestrel implant and newly diagnosed lower extremity sarcoma and DVT desiring oocyte cryopreservation prior to adjuvant chemotherapy and radiation. To avoid delay in her oncologic care and allow for continued use of contraception post-retrieval, the patient underwent controlled ovarian hyperstimulation (COH) without removal of the etonogestrel implant. RESULTS: Baseline labs included follicle-stimulating hormone 9 mIU/mL, luteinizing hormone 4.9 mIU/mL, estradiol 42 pg/mL, anti-Müllerian hormone 5.1 ng/mL, and antral follicle count greater than 40. The patient was placed on an antagonist protocol and stimulated with 125 IU Gonal-F and 75 IU Menopur. She received a total of 12 days of gonadotropin stimulation. On the day of trigger, her estradiol was 1472 pg/mL, lead follicle 21.5 mm with a total of 25 follicles measured > 12 mm. She was triggered with 5000 U hCG. She had a total of 23 oocytes retrieved, 17 of which were metaphase II and vitrified. CONCLUSIONS: COH and successful oocyte cryopreservation can be achieved in patients with an etonogestrel implant in situ without apparent detrimental effects to oocyte yield or maturity. Due to the etonogestrel implant's inhibitory effects on LH, it is recommended to use an hCG trigger for final oocyte maturation.

The Menopause Transition: Signs, Symptoms, and Management Options.

CONTEXT: Menopause, the permanent cessation of menses, reflects oocyte depletion and loss of gonadal steroids. It is preceded by a transition state, the perimenopause, which is characterized by the gradual loss of oocytes, altered responsiveness to gonadal steroid feedback, wide hormonal fluctuations, and irregular menstrual patterns. The goal of this mini-review is to discuss the basic pathophysiology of the menopausal transition and the hormonal and nonhormonal management of clinicopathology attributed to it. EVIDENCE ACQUISITION: A Medline search of epidemiologic, population-based studies, and studies of reproductive physiology was conducted. A total of 758 publications were screened. EVIDENCE SYNTHESIS: The reproductive hormonal milieu of the menopausal transition precipitates bothersome vasomotor symptoms, mood disruption, temporary cognitive dysfunction, genitourinary symptoms, and other disease processes that reduce the quality of life of affected women. The endocrine tumult of the menopause transition also exposes racial and socioeconomic disparities in the onset, severity, and frequency of symptoms. Hormone therapy (HT) treatment can be effective for perimenopausal symptoms but its use has been stymied by concerns about health risks observed in postmenopausal HT users who are older than 60 and/or women who have been postmenopausal for greater than 10 years. CONCLUSIONS: The menopause transition is a disruptive process that can last for over a decade and causes symptoms in a majority of women. It is important for clinicians to recognize early signs and symptoms of the transition and be prepared to offer treatment to mitigate these symptoms. Many safe and effective options, including HT, are available.

Birth outcomes are superior after transfer of fresh versus frozen embryos for donor oocyte recipients.

STUDY QUESTION: For donor oocyte recipients, are birth outcomes superior for fresh versus frozen embryos? SUMMARY ANSWER: Among fresh donor oocyte recipients, fresh embryos are associated with better birth outcomes when compared with frozen embryos. WHAT IS KNOWN ALREADY: Frozen embryo transfer (ET) with vitrification has been associated with improved pregnancy rates, but also increased rates of large for gestational age infants. Donor oocyte recipients represent an attractive biological model to attempt to isolate the impact of embryo cryopreservation on IVF outcomes, yet there is a paucity of studies in this population. STUDY DESIGN, SIZE, DURATION: A retrospective cohort of the US national registry, the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, of IVF cycles of women using fresh donor oocytes resulting in ET between 2013 and 2015. Thawed oocytes were excluded. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Good obstetric outcome (GBO), defined as a singleton, term, live birth with appropriate for gestational age birth weight, was the primary outcome measure. Secondary outcomes included live birth, clinical pregnancy, spontaneous abortion, preterm birth, multiple births and gestational age-adjusted weight. Outcomes were modeled using the generalized estimating equation approach. MAIN RESULTS AND THE ROLE OF CHANCE: Data are from 25 387 donor oocyte cycles, in which 14 289 were fresh and 11 098 were frozen ETs. A GBO was 27% more likely in fresh ETs (26.3%) compared to frozen (20.9%) (adjusted risk ratio 1.27; 95% confidence interval (CI) 1.21-1.35; P < 0.001). Overall, fresh transfer was more likely to result in a live birth (55.7% versus 39.5%; adjusted risk ratio 1.21; 95% CI 1.18-1.26; P < 0.001). Among singleton births, there was no difference in gestational age-adjusted birth weight between groups. LIMITATION, REASONS FOR CAUTION: Our cohort findings contrast with data from autologous oocytes. Prospective studies with this population are warranted. WIDER IMPLICATIONS OF THE FINDINGS: Among donor oocyte recipients, fresh ETs may be associated with better birth outcomes. Reassuringly, given its prevalent use, modern embryo cryopreservation does not appear to result in phenotypically larger infants. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Preimplantation genetic testing and chances of a healthy live birth amongst recipients of fresh donor oocytes in the United States.

PURPOSE: To evaluate if preimplantation genetic testing (PGT) improves the odds of a healthy live birth amongst recipients of fresh donor oocytes. METHODS: We performed a retrospective cohort study including in vitro fertilization cycles of women using fresh donor oocytes reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, between 2013 and 2015. Cycles were categorized based on PGT. Primary outcome measure was a good birth outcome (GBO), defined as a singleton, term, live birth with an average birthweight. Multivariable generalized estimating equation models were fit to analyze the effect of PGT. Interaction effect between cycle type (fresh vs frozen) and PGT was tested. RESULTS: Of 28,153 included cycles, 3708 had PGT while 24,445 did not. PGT cycles were less likely to result in an embryo transfer (ET) (64 vs 94%), but were associated with increased rates of frozen ET (70 vs 41%), single ET (67 vs 44%), and blastocyst ET (87 vs 65%). There was a significant interaction between PGT and cycle type. Cycles using PGT increased the probability of a GBO 12% in frozen cycles (RR 1.12; 95% CI 1.02, 1.22; p = 0.018), but PGT was detrimental to success in fresh cycles with a 53% reduced likelihood of GBO (RR 0.47; 9% CI 0.41, 0.54; p < 0.001). CONCLUSION: PGT, as practiced during the most recently available national data in women using fresh donor oocytes, was associated with increased probability of a healthy live birth amongst frozen cycles, but was not beneficial in fresh cycles.

Recommendations for assessing ovarian health and fertility potential in survivors of childhood cancer.

Most children diagnosed with cancer survive for many years after treatment. However, the fertility potential of these patients may suffer due to their oncologic therapies. Certain chemotherapies and radiation are more likely to be detrimental to gonadal function, and put patients at risk of acute or premature ovarian failure. Prepubertal cancer patients will need different follow-up and testing from their post-pubertal counterparts. This review will present evidence to help patients, family members and physicians determine who is most at risk of ovarian insufficiency and how to monitor childhood cancer survivors. It will discuss the impact of age at diagnosis and cancer therapies on reproductive outcomes, and guide caregivers and patients on monitoring gonadal function after therapy.

Assessing access to assisted reproductive services for serodiscordant couples with human immunodeficiency virus infection.

OBJECTIVE: To understand the barriers that serodiscordant couples with human immunodeficiency virus (HIV) face in accessing services for risk reduction and infertility using assisted reproductive technology (ART). DESIGN: Two-arm cross-sectional telephone "secret shopper" study. SETTING: Infertility clinics designated by the Society for Assisted Reproductive Technology (SART), 140 from 15 American states with the highest prevalence of heterosexual HIV-infected men. PATIENT(S): Clinical and nonclinical staff at SART-registered clinics. INTERVENTION(S): Standardized telephone calls to SART-registered clinics by investigators in the roles of physician and patient callers. MAIN OUTCOME MEASURE(S): Availability and difference in services offered to callers and the rate of referral if the clinic did not provide these services. RESULT(S): Of the 140 sampled SART clinics across 15 states, callers in both patient and physician roles spoke to a staff member at greater than 90% of targeted clinics (127 clinics total). Of the physician callers 63% were told that the clinic could offer services, as compared to 40% of patient callers. Of the 55 clinics that were unable to provide services to the patient caller, 51% referred to other clinics with confidence that they could offer these services; 67% of clinics would provide services for both prevention and infertility purposes. CONCLUSION(S): Risk reduction services for HIV were more available at the sampled fertility clinics than previously reported in the literature. However, the responses depended on the person calling. The clinics demonstrated low rates of concordance with the American Society for Reproductive Medicine's guidelines, which endorse referral of patients to other facilities from sites unable to offer services.

Pathologically Diagnosed Placenta Accreta and Hemorrhagic Morbidity in a Subsequent Pregnancy.

OBJECTIVE: To identify the relationship between pathologically diagnosed placenta accreta and risk of major morbidity in a subsequent pregnancy. METHODS: We conducted a retrospective cohort study of patients with pathologically diagnosed placenta accreta in an index pregnancy who returned with a subsequent pregnancy at our academic center from 2007 to 2015. Subsequent delivery outcomes included minor, major, or no morbidity. Minor morbidity included estimated blood loss 500-1,500 cc for vaginal and 1,000-1,500 cc for cesarean delivery, transfusion of one to three units of red cells, and minor surgical procedures. Major morbidity included estimated blood loss greater than 1,500 cc, transfusion of greater than three units of red cells, uterine artery embolization, unplanned laparotomy, or hysterectomy. RESULTS: Three hundred thirty-nine patients with pathologically diagnosed accreta did not undergo hysterectomy, and 39 (11.5%) of these returned for subsequent delivery. Of these, 14 (36%) had accretas that had been identified clinically in the index pregnancy. Twenty-one (54%) experienced morbidity in the index pregnancy, 16 of these (76%) minor and five (24%) major. Of patients without morbidity in the first pregnancy, none experienced major morbidity in a subsequent pregnancy, whereas 6 of 21 (29%) with any index morbidity had a subsequent major morbid outcome (P=.02). Of those with a morbid index delivery, 25% had either a clinical or pathologic accreta diagnosis at follow-up compared with none of those who index accreta was nonmorbid (P=.05). CONCLUSION: Risk for major hemorrhagic morbidity after a prior pathologically diagnosed accreta depends on the clinical context. Preparation for major blood loss is indicated after any prior pregnancy complicated by hemorrhage or treatment of retained placenta with a pathologic accreta.

Prospective, randomized, double-blind clinical study evaluating the correlation of clinical outcomes and cervical sagittal alignment.

BACKGROUND: Sagittal alignment of the cervical spine has received increased attention in the literature as an important determinant of clinical outcomes after anterior cervical diskectomy and fusion. Surgeons use parallel or lordotically fashioned grafts depending on preference or simple availability. OBJECTIVE: To quantitatively assess and compare cervical sagittal alignment and clinical outcome when lordotic or parallel allografts were used for fusion. METHODS: A prospective, randomized, double-blind clinical study that enrolled 122 patients was performed. The mean follow-up was 37.5 months (range, 12-54 months). RESULTS: The mean postoperative cervical sagittal alignment was 19° (range, -7°-36°) and 18° (range, -7°-37°) in the lordotic and parallel graft patient groups, respectively. The mean segmental sagittal alignment was 6° (range, -4°-19°) and 7° (range, -3°-19°) in the lordotic and parallel graft patient groups, respectively. There were no statistically significant differences in clinical outcome scores between the lordotic and parallel graft patient groups. However, patients who had maintained or improved segmental sagittal alignment, regardless of graft type, achieved a higher degree of improvement in Short Form-36 Physical Component Summary and Neck Disability Index scores. This was statistically significant (P < .038). CONCLUSION: The use of lordotically shaped allografts does not increase cervical/segmental sagittal alignment or improve clinical outcomes. Maintaining a consistent segmental sagittal alignment or increasing segmental lordosis was related to a higher degree of improvement in clinical outcomes.

Increased proinflammatory and oxidant gene expression in circulating mononuclear cells in older adults: amelioration by habitual exercise.

We tested the hypothesis that peripheral blood mononuclear cells (PBMC) of older adults demonstrate a proinflammatory/-oxidative gene expression profile that can be improved by regular aerobic exercise. PBMC were isolated from young (n = 25, 18-33 yr) and middle-aged/older (n = 40, 50-76 yr) healthy adults. The older adults had greater mRNA expression (real-time RT-PCR) of the proinflammatory/-oxidant transcription factor nuclear factor-κB (1.58-fold, P < 0.05) and receptor for advanced glycation end products (1.12-fold, P < 0.05), the proinflammatory cytokines tumor necrosis factor-α (1.90-fold, P < 0.05) and monocyte chemoattractant protein-1 (1.47-fold, P < 0.05), and the oxidant-producing enzymes nicotinamide adenine dinucleotide phosphate-oxidase (0.91-fold, P < 0.05) and inducible nitric oxide synthase (2.60-fold, P < 0.05). In 11 subjects (58-70 yr), maximal oxygen consumption (+11%) and exercise time (+19%) were increased (both P < 0.001), and expression of the above proinflammatory/-oxidative genes was or tended to be decreased in PBMC after vs. before 2 mo of aerobic exercise (brisk walking ∼6 days/wk, 50 min/day, 70% of maximal heart rate). Expression of interleukin-6 was not different with age or exercise intervention. Age group- and exercise intervention-related differences in gene expression were independent of other factors. PBMC of healthy older adults demonstrate increased expression of several genes associated with inflammation and oxidative stress, which is largely ameliorated by habitual aerobic exercise. This proinflammatory/-oxidative gene signature may represent a therapeutic target for lifestyle and pharmacological prevention and treatment strategies.

Minimally invasive versus open transforaminal lumbar interbody fusion.

BACKGROUND: Available clinical data are insufficient for comparing minimally invasive (MI) and open approaches for transforaminal lumbar interbody fusion (TLIF). To date, a paucity of literature exists directly comparing minimally invasive (MI) and open approaches for transforaminal lumbar interbody fusion (TLIF). The purpose of this study was to directly compare safety and effectiveness for these two surgical approaches. MATERIALS AND METHODS: Open or minimally invasive TLIF was performed in 63 and 76 patients, respectively. All consecutive minimally invasive TLIF cases were matched with a comparable cohort of open TLIF cases using three variables: diagnosis, number of spinal levels, and history of previous lumbar surgery. Patients were treated for painful degenerative disc disease with or without disc herniation, spondylolisthesis, and/or stenosis at one or two spinal levels. Clinical outcome (self-report measures, e.g., visual analog scale (VAS), patient satisfaction, and MacNab's criteria), operative data (operative time, estimated blood loss), length of hospitalization, and complications were assessed. Average follow-up for patients was 37.5 months. RESULTS: The mean change in VAS scores postoperatively was greater (5.2 vs. 4.1) in theopen TLIF patient group (P = 0.3). MacNab's criteria score was excellent/good in 67% and 70% (P = 0.8) of patients in open and minimally invasive TLIF groups, respectively. The overall patient satisfaction was 72.1% and 64.5% (P = 0.4) in open and minimally invasive TLIF groups, respectively. The total mean operative time was 214.9 min for open and 222.5 min for minimally invasive TLIF procedures (P = 0.5). The mean estimated blood loss for minimally invasive TLIF (163.0 ml) was significantly lower (P < 0.0001) than the open approach (366.8 ml). The mean duration of hospitalization in the minimally invasive TLIF (3 days) was significantly shorter (P = 0.02) than the open group (4.2 days). The total rate of neurological deficit was 10.5% in the minimally invasive TLIF group compared to 1.6% in the open group (P = 0.02). CONCLUSIONS: Minimally invasive TLIF technique may provide equivalent long-term clinical outcomes compared to open TLIF approach in select population of patients. The potential benefit of minimized tissue disruption, reduced blood loss, and length of hospitalization must be weighted against the increased rate of neural injury-related complications associated with a learning curve.