Depression, anxiety, quality of life, and infertility: a global lens on the last decade of research.

We aimed to review the global literature in the past 10 years regarding the impact of infertility on depression, anxiety, stress, and quality of life while exploring the potential clinical utility of psychosocial fertility questionnaires. PubMed, Scopus, and CINAHL were searched for English-published articles since 2013 on key search terms related to infertility, assisted reproductive technologies, and psychological terms such as depression, anxiety, mood disorders, and quality of life. The search yielded 7,947 articles, of which 366 articles were independently deemed relevant by the 3 reviewers. Anxiety, depression, and diminished quality of life are prevalent in the infertility experience of both men and women. Studies from around the world show similar experiences independent of culture.

Maternal outcomes of a cohort of pregnancies affected by non-immune hydrops fetalis.

OBJECTIVE: To describe the maternal outcomes of a prospective cohort of non-immune hydrops fetalis (NIHF) pregnancies with negative standard-of-care evaluations. METHODS: This study was a secondary analysis of a prospective cohort study of NIHF pregnancies with negative work-ups (infection, alloimmune anemia, fetomaternal hemorrhage, and chromosomal disorders). Outcomes were obstetric complications, including pre-eclampsia, mirror syndrome, preterm birth, polyhydramnios, postpartum hemorrhage, and maternal mental health. RESULTS: Forty pregnancies were included. Four patients developed pre-eclampsia (4/40, 10.0%); three occurred postpartum. None was diagnosed with mirror syndrome. Of the 31 continued pregnancies, 16 (51.6%) resulted in early fetal death or stillbirth and 15 (48.4%) resulted in live births. Of the 15 live births, 8 (53.3%) were delivered by primary cesarean delivery; 5 (62.5%) were for hydrops fetalis. Eleven live births (73.3%) were delivered preterm; 9 (81.8%) were indicated, most commonly for fetal indications (7/9, 77.8%). Polyhydramnios occurred in 14/40 (35.0%) cases. Where EBL was recorded (n=37), there were 5 (13.5%) cases of postpartum hemorrhage and an additional 3 (8.1%) had uterine atony without hemorrhage. Eighteen patients (18/40, 45.0%) had new-onset or exacerbated depression or anxiety symptoms. CONCLUSION: Our study identified several important adverse outcomes of pregnancies complicated by NIHF with negative standard-of-care evaluations, including a high rate of postpartum pre-eclampsia and worsened mental health. We identified a higher rate of cesarean delivery and preterm birth, both primarily for fetal indications. We also observed the known relationship between polyhydramnios, hemorrhage, and atony, but noted that this risk included pregnancies concluding in dilation and evacuation. Counseling after a diagnosis of NIHF should include these adverse outcomes.

RASopathies are the most common set of monogenic syndromes identified by exome sequencing for nonimmune hydrops fetalis: A systematic review and meta-analysis.

RASopathies are a group of malformation syndromes known to lead to nonimmune hydrops fetalis (NIHF) in severe presentations. Pathogenic variants can be de novo or parentally inherited. Despite being a known frequent presentation, the fraction of monogenic NIHF cases due to RASopathies is limited in the literature. Also, the specific parental contribution of RASopathies to NIHF is not well described. Our objective was to review pooled exome sequencing (ES) diagnostic yield of RASopathies for NIHF and to determine the parental contribution of RASopathy to NIHF. We performed a systematic review of prenatal ES studies from January 1, 2000 to August 1, 2022. Thirty-six studies met inclusion criteria. Cases with RASopathy gene variants were reviewed. NIHF cases were further classified as isolated or non-isolated. Thirty-six ES studies including 46 pregnancies with NIHF and a diagnosed RASopathy were reviewed. Forty-four diagnostic variants and 2 variants of uncertain significance in 12 RASopathy genes were identified. Expanding on what was previously published, a total of 506 NIHF cases were extracted with 191 cases yielding a positive diagnosis by ES. The overall rate of RASopathy diagnosis in clinically diagnosed NIHF cases was 9% (44/506). The rate of RASopathy diagnosis among NIHF cases with positive genetic diagnosis by ES was 23% (44/191). Of the 46 cases identified, 13 (28%) variants were parentally inherited; specifically, 5/13 (38%) maternal, 3/13 (23%) paternal, 2/13 (15%) biparental, and 3/13 (23%) unspecified. Majority of NIHF cases 29/46 (63%) were isolated. Among NIHF cases with positive ES diagnoses, RASopathy diagnostic yield by ES was 23%. NIHF secondary to RASopathies was parentally inherited in 28% of cases. Most cases of NIHF due to RASopathy were isolated, with no prenatal detection of associated anomalies.

Genetic counseling practices among outpatient obstetric providers in the Northeast.

BACKGROUND: The American College of Obstetricians and Gynecologists recommends all pregnant people be offered genetic screening and diagnostic testing regardless of risk factors. Previous studies have demonstrated disparities in referrals for genetic testing by race outside of pregnancy, but limited data exist regarding genetic counseling practices during pregnancy. OBJECTIVE: This study aimed to describe how patient, provider, and practice demographics influence the offering of diagnostic prenatal genetic testing by outpatient prenatal care providers. STUDY DESIGN: This was a multicenter anonymous survey study conducted between October 2021 and March 2022. Outpatient prenatal care providers, including family medicine and obstetrics attendings, residents, maternal-fetal medicine fellows, nurse practitioners, physician assistants, and midwives, were surveyed about their genetic counseling practices and practice demographics. The primary outcome was the proportion of respondents who answered "yes, all patients" to the survey question "Do you offer diagnostic genetic testing to all patients?" The secondary outcomes included the association between patient and practice demographics and offering diagnostic testing. Diagnostic testing was defined as chorionic villus sampling or amniocentesis. Screening genetic tests were defined as sequential screen, quadruple screen, cell-free DNA screening, or "other." The chi-square test or Fisher exact test was used as appropriate. For the outcome answers of diagnostic testing, logistic regression was performed to assess the association between the answer of diagnostic genetic testing and the current training level of providers, race and ethnicity, and insurance status variables. Multivariable analysis was performed to adjust for confounders. RESULTS: A total of 635 outpatient prenatal care providers across 7 sites were sent the survey. Overall, 419 providers responded for a total response rate of 66%. Of the providers who responded, most were attendings (44.9%), followed by residents (37.5%). Providers indicated the race, insurance status, and primary language of their patient population. Screening genetic testing was offered by 98% of providers. Per provider report, 37% offered diagnostic testing to all patients, 18% did not offer it at all, and 44% only offered it if certain patient factors were present. Moreover, 54.8% of attendings reported universally offering diagnostic testing. On univariable analysis, residents were less likely to offer diagnostic testing than attendings (odds ratio, 0.18; 95% confidence interval, 0.11-0.30). Providers who serve non-Hispanic Black, Hispanic Black, and other Hispanic patients were less likely to report offering diagnostic testing than other patient populations. Providers who served non-Hispanic Whites were more likely to offer diagnostic testing (odds ratio, 2.26; 95% confidence interval, 1.51-3.39). Patient populations who were primarily privately insured were more likely to be offered diagnostic testing compared with primarily publicly insured patients (odds ratio, 6.25; 95% confidence interval, 3.60-10.85). Providers who served a primarily English-speaking population were more likely to offer diagnostic genetic testing than other patient populations (odds ratio, 0.43; 95% confidence interval, 0.26-0.69). On multivariable analysis, the factors that remained significantly associated with offering diagnostic testing included level of training (resident odds ratio, 0.33; 95% confidence interval, 0.17-0.62; P=.0006; advanced practice provider odds ratio, 0.34; 95% confidence interval, 0.15-0.82; P=.02), having at least one-third of the patient population identify as "other Hispanic" (odds ratio, 0.42; 95% confidence interval, 0.23-0.77; P=.005), and having private insurance instead of public insurance (primarily private insured odds ratio, 2.84; 95% confidence interval, 1.20-6.74; P=.02). CONCLUSION: Although offering genetic screening and diagnostic testing to all patients is recommended, no provider group universally offers diagnostic testing. Providers who serve populations from a racial and ethnic minority, those with public insurance, and those whose primary language is not English are less likely to report universally offering diagnostic genetic testing.

Management of a Retained Broken Suture Needle During Cerclage Placement.

BACKGROUND: Broken suture needles with unintentional foreign body retention are an uncommon occurrence during obstetric procedures. Few reports exist in the literature of cases in pregnant patients. We report a case with the pregnancy management of a broken needle during cerclage placement that was retained in the cervix until repeat cesarean delivery. CASE: A 36-year-old woman, gravida 12 para 5, presented at 13 weeks of gestation for a history-indicated cerclage. The suture needle broke during the cerclage procedure, leaving a 35-mm needle fragment inside the cervical stroma between the 11 and 2 o'clock position that could not be recovered after multiple attempts. The procedure continued without needle recovery. Intraoperative pelvic X-ray was performed, demonstrating the retained fragment. No further attempts at recovery were made during the pregnancy, and a plan was made to proceed with removal at the patient's repeat cesarean delivery. The patient presented in labor at 32 1/7 weeks of gestation and underwent an uncomplicated cesarean delivery. The retained needle was subsequently removed after manual palpation of the fragment transvaginally. CONCLUSION: Retained broken suture needles during obstetric procedures require careful management decisions in pregnant patients. Retention of a needle fragment until delivery may be considered if risks of removal outweigh the anticipated benefits.

Sperm donor attitudes and experiences with direct-to-consumer genetic testing.

Objective: To identify factors influencing sperm donor willingness to participate in direct-to-consumer genetic testing, comfort with sharing genetically identifiable data in commercial genetic testing databases, and likelihood to donate sperm again. Design: Cross-sectional online anonymous survey. Setting: Multicenter, 2 large American sperm banks from July 1, 2020 to July10, 2021. Patients: Sperm donors from 1980 to 2020. Interventions: None. Main outcome measures: Associations between donor demographic characteristics, donation history, and attitudes toward direct-to-consumer genetic testing. Results: A total of 396 donors completed the survey. Most donations (61.5%) occurred from 2010 to 2020, and 34.3% were nonidentified donations. Nonidentified donors were less comfortable with their genetic data being shared than open-identity donors (25.4% vs. 43.8%) and were less likely than open-identity donors to donate sperm again (43.3% vs. 72.1%). Donors who donated after the inception of direct-to-consumer genetic testing in 2007 were less likely to participate in commercial genetic testing than those who donated before 2007 (25.8% vs. 37.1%). Most donors (87.4%) have disclosed their donation(s) to current partners, but fewer have disclosed them to their families (56.6%) or children (30.5%). Of the donors who had been contacted by donor-conceived persons, 79.5% were identified via direct-to-consumer genetic testing. Overall, 61.1% of donors would donate again regardless of direct-to-consumer genetic testing. Conclusions: Direct-to-consumer genetic testing is playing a dynamic role in sperm donor identification, but donors seem willing to donate again. Implication counseling regarding future linkage and contact from donor-conceived persons needs to be standardized for potential donors before donation.

Diagnostic yield from prenatal exome sequencing for non-immune hydrops fetalis: A systematic review and meta-analysis.

Non-immune hydrops fetalis (NIHF) has multiple genetic etiologies diagnosable by exome sequencing (ES). We evaluated the yield of prenatal ES for NIHF, and the contribution of additional clinical findings and history. Systematic review was performed with PROSPERO tag 232951 using CINAHL, PubMed, and Ovid MEDLINE from January 1, 2000 through December 1, 2021. Selected studies performed ES to augment standard prenatal diagnostic approaches. Cases meeting a strict NIHF phenotype were tabulated with structured data imputed from papers or requested from authors. Genetic variants and diagnostic outcomes were harmonized across studies using current ACMG and ClinGen variant classification guidelines. Thirty-one studies reporting 445 NIHF cases had a 37% (95% CI: 32%-41%) diagnostic rate. There was no significant difference between isolated NIHF and NIHF with fetal malformations or between recurrent and simplex cases. Diagnostic rate was higher for consanguineous than non-consanguineous cases. Disease categories included RASopathies (24%), neuromuscular (21%), metabolic (17%), lymphatic (13%), other syndromes (9%), cardiovascular (5%), hematologic (2%), skeletal (2%), and other categories (7%). Inheritance patterns included recessive (55%), dominant (41%), and X-linked (4%). ES should be considered in the diagnostic workup of NIHF with and without associated ultrasound findings regardless of history of recurrence or consanguinity.

A Systematic Review of Reproductive Counseling in Cases of Parental Constitutional Reciprocal Translocation (9;22) Mimicking BCR-ABL1.

We aim to determine the spectrum of cytogenetic abnormalities and outcomes in unbalanced offspring of asymptomatic constitutional balanced t(9;22) carriers through a systematic literature review. We also include a case of a constitutional balanced t(9;22) carrier from our institution. Among the 16 balanced t(9;22) carriers in our review, 13 were maternal and 3 were paternal. Of the 15 unbalanced translocation cases identified, 13 were live births, one was a missed abortion, and one resulted in pregnancy termination. The spectrum of established syndromes reported among the live births was the following: trisomy 9p syndrome (6/13), dual trisomy 9p and DiGeorge syndrome (3/13), dual 9q subtelomere deletion syndrome and DiGeorge syndrome (1/13), 9q subtelomere deletion syndrome (1/13), and DiGeorge syndrome (1/13). One unbalanced case did not have a reported syndrome. The phenotype of the unbalanced cases included cardiac abnormalities (5/13), neurological findings (7/13), intellectual disability (6/10), urogenital anomalies (3/13), respiratory or immune dysfunction (3/13), and facial or skeletal dysmorphias (13/13). Any constitutional balanced reciprocal t(9;22) carrier should be counseled regarding the increased risk of having a child with an unbalanced translocation, the spectrum of possible cytogenetic abnormalities, and predicted clinical phenotype for the unbalanced derivative.

Fetal pharmacogenomics: A promising addition to complex neonatal care.

OBJECTIVE: Pharmacogenomics (PGx) characterizes genetic variation in medication response. 85-95% of the population carries actionable PGx variants. No prior studies have demonstrated the application and feasibility of PGx in prenatal testing. We assessed parental desire for PGx findings from fetal exome sequencing (ES), evaluated PGx variants, and reviewed implications for medically complex neonates. METHODS: A prospective cohort undergoing ES for nonimmune hydrops fetalis were offered PGx results as a secondary finding. Seven pharmacogenes with Level A evidence, defined by Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, were tested and reported to patients and referring providers. Medication administration records were reviewed. RESULTS: Most participants (36/40, 90%) desired PGx testing. 32/36 (89%) had potentially actionable PGx diplotypes in six genes: CYP2C19 (20/36, 56%), CYP2C9 (16/36, 44%), CYP2D6 (10/36, 28%), SLCO1B1 (13/36, 36%), TPMT (6/36, 17%), UGT1A1 (4/36, 11%). 12/13 (92%) live births had PGx variants. Neonatal chart review indicated that three medications with CPIC Level A evidence were administered to four neonates. None of the patients received a medication that aligned with an actionable pharmacogenetic variant as defined by Level A CPIC guidance. CONCLUSION: Most participants opted to receive PGx results. 89% had actionable variants, consistent with population estimates. Obtaining fetal PGx data is feasible for medically complex neonates. Further studies are needed for broad clinical application of PGx in fetuses with major congenital abnormalities. Our study demonstrates the potential of PGx as useful preemptive clinical information that could be obtained at the time of fetal exome sequencing for other indications. CLINICALTRIALS: gov Registration: NCT03911531.

Outpatient maternity care and telemedicine use perceptions in the COVID-19 pandemic: a 2020 CERA survey.

The COVID-19 pandemic resulted in rapid telemedicine implementation. This study aimed to identify mean differences in telehealth maternity care provided by perceived patient acceptability and clinician satisfaction, and to determine the association between acceptability, satisfaction, and perceived anticipation of long-term telehealth utilization in family medicine maternity care. Data from the 2020 Council of Academic Family Medicine Educational Research Alliance general membership survey of family medicine educators and practicing clinicians were analyzed. Respondents who reported providing maternity care in the 12 months preceding the survey were included (N = 290). Descriptive statistics were calculated. ANOVA was used to determine the mean difference in percent maternity care provided by reported clinician satisfaction and perceived patient acceptability. Logistic regression models were fit to determine associations between perceived telehealth satisfaction and acceptability with long-term use. The sample was 67 percent female, 85 percent white, mean age of 45 years (SE = .63). 51 percent reported total prenatal visits decreased since pandemic onset. Greater agreement with perceived patient telehealth acceptability (OR = 3.73 , 95 percent CI 1.09, 12.71) and clinician telehealth satisfaction (OR = 3.72 , 95 percent CI 1.40, 9.86) was significantly associated with anticipated long-term usage. Perceived patient telehealth acceptance and clinician satisfaction were significantly higher among clinicians providing more telehealth and positively associated with anticipated long-term use.