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OBJECTIVE: To evaluate the predictive value of sperm morphology, specifically teratospermia, seen during initial semen analysis on the success of intrauterine insemination (IUI) cycles and pregnancy outcomes. METHODS: A retrospective cohort analysis on patients undergoing IUI at a large US fertility network. Baseline demographic characteristics, primary infertility diagnoses, and pregnancy outcomes were recorded. A total of 27,925 IUI cycles in 16,169 unique patients were analyzed. IUI cycles were grouped by a sperm morphology of 1% (n=3,799), 2% (n=5,506), 3% (n=4,857), or 4% or greater (n=13,763). The outcome measures were pregnancy rate (positive pregnancy test), clinical pregnancy rate (ultrasound confirmation of a gestational sac with a yolk sac around 5-6 weeks), live birth rate, and miscarriage rate. RESULTS: Sperm morphology is a significant predictor of pregnancy rate (p= <0.001), clinical pregnancy rate (p=0.011), and live birth rate (p=0.026) following IUI. In each of these outcome measures, patients with 1% normal forms had the lowest percentage of success, and patients with 4% or greater normal forms had the most success. Relative outcome percentages, however, were similar in each group. Live birth rates in the 1%, 2%, 3% and > 4% group were 12.3%, 13.1%, 12.7% and 13.9%, respectively. Sperm morphology is not a significant predictor of miscarriage rate per clinical pregnancy post IUI (p=0.054). CONCLUSIONS: Sperm morphology was a statistically significant predictor of pregnancy, clinical pregnancy, and live birth but not miscarriage rate after an IUI cycle. Higher morphology percentages were associated with increasingly favorable outcomes. However, the small observed differences did not demonstrate clinical significance.
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OBJECTIVE: To evaluate differences in reproductive and neonatal outcomes on the basis of the time interval from cesarean delivery to subsequent frozen embryo transfer (FET). DESIGN: Retrospective cohort. SETTING: Multicenter fertility practice. PATIENTS: Women undergoing autologous elective single embryo transfer FET after prior cesarean delivery. INTERVENTION: Time from prior cesarean delivery to subsequent FET. MAIN OUTCOME MEASURES: live birth (LB). RESULTS: A total of 6,556 autologous elective single embryo transfer FET cycles were included. Frozen embryo transfer cycles were divided into eight groups on the basis of the time interval from prior cesarean delivery to subsequent FET in months. A secondary analysis was then performed with time as a continuous variable. The proportion of LBs did not differ significantly across all time interval groups and over continuous time (range: 40.0%-45.6%). The mean gestational age at the time of delivery did not significantly differ as the time between prior cesarean delivery and subsequent FET increased (range: 37.3-38.4). When time was evaluated continuously, the proportion of preterm births was higher with a shorter time between cesarean delivery and subsequent FET. The mean birth weight ranged from 3,181-3,470g, with a statistically significant increase over time. However, the proportions of extremely low birth weight, very low birth weight, and low birth weight did not significantly differ. CONCLUSION: There were no significant differences in reproductive outcomes on the basis of the time interval from cesarean delivery to FET, including LB. The proportion of preterm deliveries decreased with a longer time between cesarean delivery and FET. Differences in mean neonatal birth weight were not clinically significant because the proportion of low birth weight neonates was not significantly different over time. Although large, this sample cannot address all outcomes associated with short interpregnancy intervals, particularly rarer outcomes such as uterine rupture. When counseling patients, the timing of FET after cesarean delivery must be balanced against the risks of increasing maternal age on reproductive and neonatal outcomes.
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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.
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Transferencia de Embrión , Estradiol , Fertilización In Vitro , Nacimiento Vivo , Inducción de la Ovulación , Índice de Embarazo , Progesterona , Humanos , Femenino , Estradiol/sangre , Transferencia de Embrión/métodos , Embarazo , Adulto , Fertilización In Vitro/métodos , Inducción de la Ovulación/métodos , Progesterona/sangre , Nacimiento Vivo/epidemiología , Resultado del EmbarazoRESUMEN
OBJECTIVE: To study the primary objective of clinical pregnancy (CP) rate per ovarian stimulation with intrauterine insemination (OS-IUI) treatment cycle in patients with repetitive cycles up to a maximum of 8 cycles. DESIGN: Retrospective cohort. SETTING: Large fertility clinic. PATIENTS: A total of 37,565 consecutive OS-IUI cycles from 18,509 patients were included in this study. INTERVENTIONS: Those with anovulatory diagnoses, tubal factor infertility, male factor infertility, using donor sperm, canceled cycles, and those with missing data for either baseline characteristics or outcome were excluded. The CP rate was analyzed using generalized estimating equations and controlled for age, stimulation protocol, and body mass index. MAIN OUTCOMES MEASURES: Clinical pregnancy was defined as intrauterine gestation with fetal heartbeat visible on ultrasound. RESULTS: A total of 37,565 consecutive OS-IUI cycles from 2002 through 2019 at a private practice facility were evaluated. All cycles met inclusion criteria and were used in generalized estimating equation modeling. Patients aged <35 years comprised 47.6% of the cohort. After adjustment for confounders, the mean predicted probability of CP for cycles one to 8 was 15.7% per cycle. The mean predicted probability of CP in aggregated data from cycles 2 to 4 was only 1.7% lower compared with cycle 1 as the referent (16.7% vs. 15.0%, 95% confidence interval [CI] 2nd: 0.88 {0.82, 0.95}, 3rd: 0.86 {0.79, 0.93}, 4th: 0.88 {0.79, 0.98}). However, the 15.0% mean predicted probability of CP for the second through the fourth cycle was concordant with the mean for all included cycles (15.7%). The mean predicted probability of CP of cycles 5 to 8 was not significantly different compared with the referent (16.7% vs. 16.1%, 95% CI 5th: 0.97 [0.85, 1.11], 6th: 0.93 [0.79, 1.10], 7th: 1.01 [0.81, 1.26], 8th: 1.01 [0.76, 1.34]). The modeling of consecutive cycles suggested that the adjusted cumulative predicted probability of CP from OS-IUI continues to increase with each of the 8 successive cycles. CONCLUSION: Clinical pregnancy rates are satisfactory in up to 8 consecutive OS-IUI treatment cycles. These data are useful for counseling, especially in those patients for whom in vitro fertilization is not financially or ethically feasible.
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Fertilización In Vitro , Inseminación Artificial , Inducción de la Ovulación , Índice de Embarazo , Humanos , Femenino , Embarazo , Adulto , Estudios Retrospectivos , Inducción de la Ovulación/métodos , Fertilización In Vitro/métodos , Inseminación Artificial/métodos , Infertilidad/terapia , Infertilidad/fisiopatología , Infertilidad/diagnóstico , Resultado del Tratamiento , MasculinoRESUMEN
OBJECTIVES: To identify patient clusters based on baseline demographics and clinical indicators. METHODS: Pooled baseline demographics and clinical data of secukinumab-treated patients from ten Phase III studies in psoriatic arthritis (PsA; FUTURE 1-5 and MAXIMISE), ankylosing spondylitis (AS; MEASURE 1-4), were analysed by machine learning (ML) algorithms. The longitudinal responses of secukinumab 300 mg versus 150 mg were investigated across the clusters and three clinical indicators of tender joints, swollen joints and enthesitis. RESULTS: 3907 patients were grouped into eight distinct clusters based on patient demographics and baseline clinical characteristics. Patients with PsA and axial manifestations (MAXIMISE) were overrepresented in clusters 6-8. Patients in cluster 6 (mean age 48 years; 46% male) were overweight with pronounced psoriasis, higher articular burden in knees, shoulders, elbows and wrists. Patients in cluster 7 (mean age 47 years; 53% male) were less overweight with lower polyarticular joint counts and tenderness of the joints of the feet, wrists and hands. Patients in cluster 8 were predominantly with AS (mean age 43 years; 64% male) with a mean body mass index of 27.3 kg/m2, oligoarthritis and high prevalence of spinal pain. Patients with PsA (FUTURE) were overrepresented in clusters 1-5. Longitudinal analysis showed improvements with secukinumab 300 mg versus 150 mg in clusters 6 and 8 for tender joint counts, and cluster 7 for swollen joint counts. CONCLUSIONS: PsA clusters obtained by ML in pooled dataset indicate phenotypical heterogeneity of patients with PsA and axial manifestations and overlapping features across the spondyloarthritis spectrum.
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Artritis Psoriásica , Espondilitis Anquilosante , Humanos , Masculino , Persona de Mediana Edad , Adulto , Femenino , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/tratamiento farmacológico , Espondilitis Anquilosante/diagnóstico , Espondilitis Anquilosante/tratamiento farmacológico , Sobrepeso , Anticuerpos Monoclonales Humanizados/uso terapéuticoRESUMEN
PURPOSE: Assess the rate, rationale, and characteristics of patients who cryopreserved and subsequently discarded their oocytes, and compare their characteristics to patients with continued cryopreservation of oocytes. METHODS: All patients who disposed of cryopreserved oocytes between 2009 and 2022 reported their reason for discarding their oocytes. This was a retrospective cohort study. RESULTS: Of 5,010 patients who underwent oocyte cryopreservation (OC) cycles, 201 (4%) patients elected to discard their oocytes and 751 (15%) thawed oocytes for clinical use. The average ages of OC and disposal were 35 and 39 years old, respectively. Of the 201 patients who discarded their oocytes, 71 patients (35%) requested disposal after having a child. Twenty-six (13%) discarded oocytes because of worsening cancer and three (1.4%) discarded because of death. 16 (8%) discarded oocytes due to cost of cryopreservation and eight (4%) due to low oocyte yield. Ten (5%) patients underwent new IVF cycles and discarded previously stored oocytes. Sixty-seven patients (33%) discarded oocytes for unspecified reasons. When comparing patients who discarded oocytes with those who did not, the former had lower AMH (2.7 vs 3.5 ng/ml, p < 0.001) but otherwise comparable age and number of cryopreserved oocytes. The mean age for those with continued cryopreservation was 35.4 years at time of OC and 40 years at time of data collection in June 2023. CONCLUSION: Childbirth was the most common reason to dispose of oocytes followed by unspecified reasons. Larger studies of oocyte disposal may better define clinical characteristics of patients most likely to use, maintain or discard their oocytes.
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Preservación de la Fertilidad , Neoplasias , Niño , Humanos , Adulto , Estudios Retrospectivos , Criopreservación , OocitosRESUMEN
The technique and platform used for preimplantation genetic testing for aneuploidy (PGT-A) have undergone significant changes over time. The contemporary technique utilizes trophectoderm biopsy followed by next-generation sequencing (NGS). The goal of this study was to explore the role of PGT-A using NGS technique exclusively in contemporary in vitro fertilization (IVF) practice. For this, we performed a retrospective analysis of a large dataset collected from the Shady Grove Fertility (SGF) multicentre practice. All autologous IVF cycles which were followed by at least one single embryo transfer (ET) (fresh and/or frozen) between January 2017 to July 2020, were included. Our study group included patients who had PGT-A and the control group included patients who did not proceed with PGT-A. The primary outcome was the live birth rate (LBR) per transfer. All age-adjusted LBR was higher in the PGT-A group than the non-PGT-A group (48.9% vs. 42.7%, p < 0.001), except in women <35 years old among single embryo frozen ETs. Similarly, LBR in the PGT-A group was higher in all ages except in women <35 years old (48.7% vs. 41.7%, p < 0.001) when all single embryos fresh and frozen ETs were included. In patients of decreased ovarian reserve, transfer of euploid embryo was associated with higher LBR (46.7% vs. 26.7%, p < 0.001) whereas miscarriages were lower in patients with unexplained infertility (9.3% vs. 11.3%, p = 0.007 and endometriosis (8.9% vs. 11.6%, p < 0.001) following euploid embryo transfer. To conclude, the transfer of euploid embryos tested via NGS PGT-A was associated with improved LBR per transfer in women ≥35 years old.
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Nacimiento Vivo , Diagnóstico Preimplantación , Embarazo , Humanos , Femenino , Adulto , Diagnóstico Preimplantación/métodos , Estudios Retrospectivos , Secuenciación de Nucleótidos de Alto Rendimiento , Transferencia de Embrión/métodos , Fertilización In Vitro , Pruebas Genéticas/métodos , Aneuploidia , BlastocistoRESUMEN
OBJECTIVE: To identify whether the serum estradiol (E2) level on the day of human chorionic gonadotropin (hCG) trigger or luteinizing hormone (LH) surge (hCG-LH) was associated with the live birth rate (LBR) during ovulation induction (OI) or controlled ovarian hyperstimulation with letrozole followed by intrauterine insemination (IUI). DESIGN: Retrospective cohort study. SETTING: Large, multicenter private practice. PATIENT(S): A total of 2,368 OI-IUI cycles in patients treated with letrozole followed by IUI were evaluated from January 1, 2014, to July 31, 2019. INTERVENTION(S): Ovulation induction with letrozole, followed by autologous IUI. MAIN OUTCOME MEASURE(S): The primary outcome measure was the LBR as a function of the serum E2 level at the time of hCG administration or LH surge, adjusting for age, body mass index, the largest follicle diameter, and the number of follicles ≥14 mm in diameter. The clinical pregnancy rate as a function of the E2 level, pregnancy rate as a function of the lead follicle diameter, and pregnancy loss rates were the secondary outcome variables. RESULT(S): A total of 2,368 cycles met the inclusion criteria. Outcomes were evaluated at the 25th (E2 level, 110 pg/mL), 50th (157 pg/mL), 75th (225 pg/mL), and 90th (319 pg/mL) percentiles. The LBRs ranged from 9.4% to 11.1% in the lower E2 cohorts and from 12.5% to 13.5% in the higher E2 cohorts. The LBR was significantly greater in the cohort of women with higher E2 levels in all percentile comparisons except for the 90th percentile. The mean periovulatory follicle diameter of ≥20 or <20 mm was not independently associated with the LBR or clinical pregnancy rate, despite a significantly higher mean E2 level in the larger follicle group. CONCLUSION(S): In letrozole OI cycles followed by IUI, lower LBRs and clinical pregnancy rates were found in women with lower E2 levels than in those with higher E2 levels at the 25th, 50th, and 75th percentile E2 level quartiles. Where possible, delaying hCG trigger until the E2 level increases after aromatase inhibition and approaches the physiologic periovulatory level may improve the pregnancy rates with letrozole followed by IUI.
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Nacimiento Vivo , Hormona Luteinizante , Embarazo , Humanos , Femenino , Letrozol , Estudios Retrospectivos , Índice de Embarazo , Gonadotropina Coriónica , Inducción de la Ovulación , Estradiol , Inseminación , Inseminación ArtificialRESUMEN
OBJECTIVE: To evaluate potential variation in the euploid blastocyst rate and live birth rate (LBR) per single frozen euploid blastocyst transfer, among 4 unique United States reproductive genetics laboratories. Analyses were limited to blastocysts derived from vitrified donor oocytes, to minimize variation in oocyte quality. DESIGN: Retrospective cohort study from 2016 to 2020. SETTING: Donor Egg Bank Database. PATIENT(S): Patients undergoing in vitro fertilization with donor oocytes. We excluded patients with uterine factor, male factor, or surgically extracted sperm. Only healthy women <34 years old were accepted as oocyte donors. INTERVENTION(S): Next generation sequencing platforms for chromosomal analysis MAIN OUTCOME MEASURE(S): Euploid blastocyst rate and LBR per euploid transfer. Secondary outcomes included the rate of aneuploidy, mosaic calls, biochemical pregnancy loss, and miscarriage rate. RESULT(S): A total of 2,633 embryos were included. Four laboratories had >200 embryos tested. Euploid blastocyst rate was significantly higher in laboratory A (73.6%) vs. B (63.3%), C (60.9%), and D (52.3%). Mosaic rate was significantly lower for Laboratories B (2.8%) and C (5.5%) vs. Laboratories A (9.9%) and D (11.5). The LBR was significantly higher in laboratory A (58.73%) vs. laboratory D (47.3%). There were no significant differences in the implantation or miscarriage rate among laboratories. CONCLUSION(S): In this large study, controlling for oocyte quality, some preimplantation genetic testing for aneuploidy (PGT-A) laboratories report a significantly higher euploid blastocyst rate with concurrent higher LBR. This type of comparison is important as it provides insight into the role of the PGT-A process in outcomes. Further research is needed to evaluate the differences in laboratory techniques and bioinformatic algorithms accounting for variable outcomes across PGT-A laboratories.
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Aborto Espontáneo , Diagnóstico Preimplantación , Embarazo , Humanos , Masculino , Femenino , Tasa de Natalidad , Aborto Espontáneo/diagnóstico , Aborto Espontáneo/genética , Estudios Retrospectivos , Diagnóstico Preimplantación/métodos , Laboratorios , Nacimiento Vivo , Semen , Pruebas Genéticas/métodos , Aneuploidia , Blastocisto , OocitosRESUMEN
Importance: Endometrial receptivity testing is purported to improve live birth following frozen embryo transfer by identifying the optimal embryo transfer time for an individual patient; however, data are conflicting. Objective: To compare live birth from single euploid frozen embryo transfer according to endometrial receptivity testing vs standardized timing. Design, Setting, and Participants: Double-blind, randomized clinical trial at 30 sites within a multicenter private fertility practice in the Eastern US. Enrollment was from May 2018 to September 2020; follow-up concluded in August 2021. Participants underwent in vitro fertilization, preimplantation genetic testing for aneuploidy, endometrial receptivity testing, and frozen embryo transfer. Those with euploid blastocyst(s) and an informative receptivity result were randomized. Exclusion criteria included recurrent pregnancy loss, recurrent implantation failure, surgically aspirated sperm, donor egg(s), and unmitigated anatomic uterine cavity defects. Interventions: The intervention group (n = 381) underwent receptivity-timed frozen embryo transfer, with adjusted duration of progesterone exposure prior to transfer, if indicated by receptivity testing. The control group (n = 386) underwent transfer at standard timing, regardless of receptivity test results. Main Outcomes and Measures: The primary outcome was live birth. There were 3 secondary outcomes, including biochemical pregnancy and clinical pregnancy. Results: Among 767 participants who were randomized (mean age, 35 years), 755 (98%) completed the trial. All randomized participants were analyzed. The primary outcome of live birth occurred in 58.5% of transfers (223 of 381) in the intervention group vs 61.9% of transfers (239 of 386) in the control group (difference, -3.4% [95% CI, -10.3% to 3.5%]; rate ratio [RR], 0.95 [95% CI, 0.79 to 1.13]; P = .38). There were no significant differences in the intervention vs the control group for the prespecified secondary outcomes, including biochemical pregnancy rate (77.2% vs 79.5%, respectively; difference, -2.3% [95% CI, -8.2% to 3.5%]; RR, 0.97 [95% CI, 0.83 to 1.14]; P = .48) and clinical pregnancy rate (68.8% vs 72.8%, respectively; difference, -4.0% [95% CI, -10.4% to 2.4%]; RR, 0.94 [95% CI, 0.80 to 1.12]; P = .25). There were no reported adverse events. Conclusions and Relevance: Among patients for whom in vitro fertilization yielded a euploid blastocyst, the use of receptivity testing to guide the timing of frozen embryo transfer, compared with standard timing for transfer, did not significantly improve the rate of live birth. The findings do not support routine use of receptivity testing to guide the timing of embryo transfer during in vitro fertilization. Trial Registration: ClinicalTrials.gov Identifier: NCT03558399.
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Técnicas de Diagnóstico Obstétrico y Ginecológico , Transferencia de Embrión , Endometrio , Fertilización In Vitro , Nacimiento Vivo , Adulto , Femenino , Humanos , Masculino , Embarazo , Transferencia de Embrión/métodos , Semen , Endometrio/fisiología , Factores de Tiempo , Pruebas Diagnósticas de RutinaRESUMEN
Objective: To provide a comprehensive and multidimensional description and conceptualization of the experiences of Black women seeking treatment for infertility. Design: Convergent parallel mixed-methods study combining retrospective chart review data and semistructured interview data. Setting: Private infertility clinic. Patients: African American/Black women between 18 and 44 years of age who presented for an initial infertility evaluation with a male partner between January 2015 and September 2019 at an infertility clinic in the metropolitan Washington D.C. area. Interventions: None. Main Outcomes: Treatment seeking. Measures: Psychobiological, clinical, and sociocultural factors. Results: Along with the psychobiological, clinical, and sociocultural domains, we understood that Black women who sought treatment for infertility were older and overweight, had complex gynecological diagnoses, and experienced infertility for long periods of time. The delay in seeking treatment was possibly because of a low perceived risk of infertility, poor understanding of treatment options, inadequate referral patterns of primary care providers, and limited social support. Further, Black women experienced delays in seeking treatment because they attempted lifestyle-based self-interventions before considering medical interventions. Facilitators to care included psychological distress, complex gynecological medical history, and finding culturally competent providers. Conclusions: The study findings show that Black women in the United States are vulnerable to disparities in healthcare delivery, especially within reproductive endocrinology. Our findings highlight areas where Black women are experiencing missed opportunities for teaching, early identification, and early referrals for infertility-related concerns. Future studies should seek to reduce barriers to infertility treatment at the clinical and policy levels.
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OBJECTIVE: To determine whether endometrial receptivity analysis (ERA) improves live births in patients with and without a history of unsuccessful frozen embryo transfers (FETs). DESIGN: Retrospective cohort study. SETTING: Large reproductive center. PATIENT(S): Patients with and without ERA before euploid single FET were included in the analysis. INTERVENTION(S): Subjects in the exposed group underwent ERA and ERA-timed FETs. Subjects in the unexposed group followed a standard protocol FET without ERA. Outcomes were compared between nonreceptive and receptive subjects undergoing an ERA-timed FET and between ERA-timed vs. standard protocol FETs. MAIN OUTCOME MEASURE(S): The primary outcome was a live birth; secondary outcomes were biochemical and clinical pregnancy rates. RESULT(S): A total of 307 ERA-timed FETs and 2,284 standard protocol FETs were analyzed. One hundred twenty-five patients (40.7%) were ERA receptive, and 182 (59.3%) were ERA nonreceptive. After adjusting for the number of the previously failed FETs, there was no difference in the proportion of receptive and nonreceptive ERA results. There were no statistically significant differences in live births in patients with ERA-receptive vs. ERA-nonreceptive results (48.8% and 41.7%, respectively; adjusted odds ratio 1.17; 95% CI, 0.97-1.40). There were no statistically significant differences in live births in patients with or without ERA testing results before FET (44.6% and 51.3%, respectively; adjusted odds ratio 0.87; 95% CI, 0.73-1.04). CONCLUSION(S): Patients with an increasing number of previous failed euploid FET cycles are not at an increased risk of a displaced window of implantation. Patients categorized as receptive vs. nonreceptive and those without ERA testing results have comparable FET success rates.
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Transferencia de Embrión , Nacimiento Vivo , Blastocisto , Criopreservación/métodos , Transferencia de Embrión/métodos , Femenino , Humanos , Embarazo , Índice de Embarazo , Estudios RetrospectivosRESUMEN
OBJECTIVE: To determine whether vaginal progesterone for programmed endometrial preparation is noninferior to intramuscular progesterone in terms of live birth rates from frozen embryo transfer (FET). DESIGN: Three-armed, randomized, controlled noninferiority trial. SETTING: Multicenter fertility clinic. PATIENT(S): A total of 1,346 volunteer subjects planning vitrified-warmed transfer of high-quality nonbiopsied blastocysts were screened, of whom 1,125 subjects were ultimately enrolled and randomly assigned to treatment. INTERVENTION(S): The subjects were randomly assigned to receive, in preparation for FET, 50 mg daily of intramuscular progesterone (control group), 200 mg twice daily of vaginal micronized progesterone plus 50 mg of intramuscular progesterone every third day (combination treatment), or 200 mg twice daily of vaginal micronized progesterone. MAIN OUTCOME MEASURE(S): The primary outcome was live birth rate per vitrified-warmed embryo transfer. The secondary outcomes were a positive serum human chorionic gonadotropin test 2 weeks after FET, biochemical pregnancy loss, clinical pregnancy, clinical pregnancy loss, total pregnancy loss, serum luteal progesterone concentration 2 weeks after FET, and patient's experience and attitudes regarding the route of progesterone administration, on the basis of a survey administered to the subjects between FET and pregnancy test. RESULT(S): A total of 1,060 FETs were completed. The live birth rate was significantly lower in women receiving only vaginal progesterone (27%) than in women receiving intramuscular progesterone (44%) or combination treatment (46%). Fifty percent of pregnancies in women receiving only vaginal progesterone ended in miscarriage. CONCLUSION(S): The live birth rate after vaginal-only progesterone replacement was significantly reduced, due primarily to an increased rate of miscarriage. Vaginal progesterone supplemented with intramuscular progesterone every third day was noninferior to daily intramuscular progesterone, offering an effective alternative regimen with fewer injections. CLINICAL TRIAL REGISTRATION NUMBER: NCT02254577.
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Criopreservación , Transferencia de Embrión , Fármacos para la Fertilidad Femenina/administración & dosificación , Fertilidad/efectos de los fármacos , Fertilización In Vitro , Infertilidad/terapia , Progesterona/administración & dosificación , Aborto Espontáneo/etiología , Administración Intravaginal , Adulto , Esquema de Medicación , Transferencia de Embrión/efectos adversos , Femenino , Fármacos para la Fertilidad Femenina/efectos adversos , Fertilización In Vitro/efectos adversos , Humanos , Infertilidad/diagnóstico , Infertilidad/fisiopatología , Inyecciones Intramusculares , Nacimiento Vivo , Embarazo , Índice de Embarazo , Progesterona/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
OBJECTIVE: To compare gestational age, birth weight (BW), and live birth rates in gestational carriers (GC) after the transfer of 1 or 2 frozen embryo(s) with or without preimplantation genetic testing for aneuploidy (PGT-A), with the understanding that several social and economic factors may motivate intended parents to request the transfer of 2 embryos and/or PGT-A when using a GC. DESIGN: Retrospective cohort study SETTING: An assisted reproductive technology practice. PATIENT(S): All frozen blastocyst transfers with GCs from 2009-2018. INTERVENTION(S): One or 2 embryo frozen embryo transfers with and without PGT-A. MAIN OUTCOME MEASURE(S): Live birth, preterm birth, and low BW. RESULTS: A total of 583 frozen embryo transfer cycles with vitrified high-grade blastocysts (grade BB or higher) to GCs were analyzed. Although the live birth rate was significantly greater in frozen embryo transfers with 2 embryos, after single embryo transfer (SET), the mean gestational age and BW of live births were statistically significantly greater than those of double embryo transfer (DET). The rate of multiple births was 1.9% for SET compared to 20.0% for DET per transfer. Only 3.8% of live births from SET experienced low BW and 0.6% had very low or extremely low BW. By comparison, 12.5% of DET live births were low BW and 5% were very low BW. After SET, 13.4% of live births were preterm, compared with 40% in DET. The analysis also included a total of 194 transfers with PGT-A compared to 389 cycles without. Overall, live births per transfer were not significantly different between these latter 2 subgroups. CONCLUSION: Frozen embryo transfer cycles in GCs with DET were associated with more preterm births and lower birth weights compared with those of SET. Intended parents and GCs should be counseled that DET is associated with greater risks of adverse pregnancy and perinatal outcomes, which mitigates higher live birth rates. The use of PGT-A did not appear to improve the live birth rate.
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Blastocisto/patología , Criopreservación , Fertilización In Vitro , Diagnóstico Preimplantación , Transferencia de un Solo Embrión , Madres Sustitutas , Peso al Nacer , Implantación del Embrión , Femenino , Fertilización In Vitro/efectos adversos , Edad Gestacional , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Nacimiento Vivo , Embarazo , Índice de Embarazo , Diagnóstico Preimplantación/efectos adversos , Nacimiento Prematuro/etiología , Estudios Retrospectivos , Factores de Riesgo , Transferencia de un Solo Embrión/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: To study the relationship between postwash total motile sperm count (TMSC) and intrauterine insemination (IUI) outcomes. DESIGN: Retrospective review SETTING: Large fertility clinic PATIENT(S): A total of 92,471 insemination cycles from 37,553 patients were included in this study. INTERVENTION(S): All stimulated clomiphene citrate, letrozole, and/or injectable gonadotropin IUI cycles performed at a single institution from 2002 through 2018 were reviewed. Generalized estimating equations (GEE) analysis was used to account for multiple cycles by individual patients and to adjust for female partner age, body mass index, and stimulation protocol. MAIN OUTCOME MEASURE(S): Successful clinical pregnancy was defined as ultrasound confirmation of an intrauterine gestational sac with fetal cardiac activity. RESULT(S): A total of 92,471 insemination cycles were available to evaluate the relationship between postwash TMSC and clinical pregnancy. Pregnancy rates were highest with TMSC of ≥9 × 106 and declined gradually as TMSC decreased. Complete data for the adjusted GEE analysis were available for 62,758 cycles. Adjusted GEE analysis among cycles with TMSC of ≥9 × 106 (n = 46,557) confirmed that TMSC in this range was unrelated to pregnancy. Conversely, TMSC was highly predictive of pregnancy (Wald χ2 = 39.85) in adjusted GEE analysis among cycles with TMSC of <9 × 106 (n = 16,201), with a statistically significant decline. CONCLUSIONS: IUI pregnancy is optimized with TMSC of ≥9 × 106, below which the rates gradually decline. Although rare, pregnancies were achieved with TMSC of <0.25 × 106. Since the decline in pregnancy is gradual and continuous, there is no specific threshold above which IUI should be recommended. Rather, these more specific quantitative predictions can be used to provide personalized counseling and guide clinical decision making.
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Fertilidad , Infertilidad/terapia , Inseminación Artificial , Recuento de Espermatozoides , Motilidad Espermática , Recuperación de la Esperma , Espermatozoides/patología , Adulto , Implantación del Embrión , Femenino , Humanos , Infertilidad/diagnóstico , Infertilidad/patología , Infertilidad/fisiopatología , Inseminación Artificial/efectos adversos , Masculino , Embarazo , Índice de Embarazo , Estudios Retrospectivos , Recuperación de la Esperma/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine whether subfertility in patients with endometriosis is due to impaired endometrial receptivity by comparing pregnancy and live-birth outcomes in women with endometriosis versus two control groups without suspected endometrial factors: noninfertile patients who underwent assisted reproduction to test embryos for a single-gene disorder and couples with isolated male factor infertility. DESIGN: Retrospective cohort. SETTING: Multicenter private practice. PATIENT(S): All patients aged 24 to 44 years undergoing euploid frozen blastocysts transfer from January 2016 through March 2018. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth, clinical pregnancies, pregnancy losses, and aneuploid rates in preimplantation genetic testing for aneuploidy cycles. RESULT(S): The analysis included 459 euploid frozen embryo transfer cycles among 328 unique patients. There were no differences in clinical pregnancy, pregnancy loss, or live-birth rates in patients with endometriosis compared with both control groups. The aneuploidy rates were lowest in the preimplantation genetic testing for monogenic disorders cohort, and the endometriosis patients had aneuploidy rates similar to those of the male factor infertility patients. CONCLUSION(S): It is unclear whether endometriosis primarily affects in vitro fertilization outcomes via oocyte quality or the endometrium. By controlling for embryo quality using euploid frozen embryo transfer cycles, we found no difference in pregnancy outcomes in patients with endometriosis compared with patients undergoing treatment for male factor infertility and noninfertile patients.
Asunto(s)
Tasa de Natalidad/tendencias , Criopreservación/tendencias , Transferencia de Embrión/tendencias , Endometriosis/epidemiología , Endometriosis/terapia , Nacimiento Vivo/epidemiología , Adulto , Blastocisto , Estudios de Cohortes , Criopreservación/métodos , Técnicas de Cultivo de Embriones/métodos , Técnicas de Cultivo de Embriones/tendencias , Transferencia de Embrión/métodos , Endometriosis/diagnóstico , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To compare clinical and ongoing pregnancy after natural cycle (NC) intrauterine insemination (IUI) versus ovarian stimulation (OS) IUI in ovulatory women undergoing therapeutic donor insemination (TDI). DESIGN: Retrospective cohort. SETTING: Single infertility center. PATIENT(S): A total of 76,643 IUI cycles in patients treated with intrauterine insemination were examined. Women undergoing TDI in the absence of diagnosed female factor infertility were included. INTERVENTION(S): NC TDI or OS TDI with either clomiphene citrate or letrozole. MAIN OUTCOME MEASURE(S): Clinical and ongoing pregnancies were analyzed by generalized estimating equations adjusting for age, body mass index, total motile sperm at time of insemination and cycle number. Ongoing multiple gestations were examined as a secondary outcome. RESULT(S): Six thousand one hundred ninety-two TDI cycles from 2,343 patients (711 patients without repeated IUI cycles) met inclusion criteria and were available for analysis (3,837 NC and 2,355 OS). There was no difference in mean age between the two groups (NC, 34.2 years vs. OS, 34.3 years). Probability of clinical and ongoing pregnancy was higher in the OS cohort compared with the NC cohort (OS, 22.4% vs. NC, 18.7% and OS, 15.4% vs. NC, 14.9%, respectively). However, OS significantly increased ongoing multiple gestations (OS, 10.8% vs. NC, 2.4%). CONCLUSION(S): Ovarian stimulation in TDI cycles resulted in a <4% increase in clinical and <1% increase in ongoing pregnancy, and more than fourfold increase in ongoing multiple gestations. Natural cycle IUI should be considered as a first-line treatment for ovulatory women who need donor insemination.
Asunto(s)
Infertilidad Femenina/terapia , Inseminación Artificial/métodos , Inducción de la Ovulación/métodos , Ovulación/fisiología , Adulto , Estudios de Cohortes , Femenino , Humanos , Infertilidad Femenina/diagnóstico , Inseminación Artificial/tendencias , Masculino , Inducción de la Ovulación/tendencias , Estudios RetrospectivosRESUMEN
STUDY QUESTION: Do donor oocyte recipients benefit from preimplantation genetic testing for aneuploidy (PGT-A)? SUMMARY ANSWER: PGT-A did not improve the likelihood of live birth for recipients of vitrified donor oocytes, but it did avoid embryo transfer in cycles with no euploid embryos. WHAT IS KNOWN ALREADY: Relative to slow freeze, oocyte vitrification has led to increased live birth from cryopreserved oocytes and has led to widespread use of this technology in donor egg IVF programs. However, oocyte cryopreservation has the potential to disrupt the meiotic spindle leading to abnormal segregation of chromosome during meiosis II and ultimately increased aneuploidy in resultant embryos. Therefore, PGT-A might have benefits in vitrified donor egg cycles. In contrast, embryos derived from young donor oocytes are expected to be predominantly euploid, and trophectoderm biopsy may have a negative effect relative to transfer without biopsy. STUDY DESIGN, SIZE, DURATION: This is a paired cohort study analyzing donor oocyte-recipient cycles with or without PGT-A performed from 2012 to 2018 at 47 US IVF centers. PARTICIPANTS/MATERIALS, SETTING, METHODS: Vitrified donor oocyte cycles were analyzed for live birth as the main outcome measure. Outcomes from donors whose oocytes were used by at least two separate recipient couples, one couple using PGT-A (study group) and one using embryos without PGT-A (control group), were compared. Generalized estimating equation models controlled for confounders and nested for individual donors contributing to both PGT-A and non-PGT-A cohorts, enabling a single donor to serve as her own control. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 1291 initiated recipient cycles from 223 donors were analyzed, including 262 cycles with and 1029 without PGT-A. The median aneuploidy rate per recipient was 25%. Forty-three percent of PGT-A cycles had only euploid embryos, whereas only 12.7% of cycles had no euploid embryos. On average 1.09 embryos were transferred in the PGT-A group compared to 1.38 in the group without PGT-A (P < 0.01). Live birth occurred in 53.8% of cycles with PGT-A versus 55.8% without PGT-A (P = 0.44). Similar findings persisted in cumulative live birth from per recipient cycle. LIMITATIONS, REASONS FOR CAUTION: Pooled clinical data from 47 IVF clinics introduced PGT-A heterogeneity as genetic testing were performed using different embryology laboratories, PGT-A companies and testing platforms. WIDER IMPLICATIONS OF THE FINDINGS: PGT-A testing in donor oocyte-recipient cycles does not improve the chance for live birth nor decrease the risk for miscarriage in the first transfer cycle but does increase cost and time for the patient. Further studies are required to test if our findings can be applied to the young infertility patient population using autologous oocytes. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.