RESUMEN
This article presents a case of spontaneous conception and live birth in a 40-year-old woman who had undergone gonadotoxic chemotherapy and allogenic stem cell transplant for relapsed acute myelogenous leukemia complicated by treatment-refractory graft-versus-host disease. The patient's follicle stimulating hormone level was 44.4 mIU/mL at age 38 and then decreased to 4.1 mIU/mL at age 41, suggesting ovarian recovery. Her graft-versus-host disease subjectively improved during pregnancy. She ultimately delivered a healthy neonate. This case demonstrates the potential for ovarian recovery after stem allogenic cell transplant in a patient of advanced reproductive age and provides insight into the limited knowledge about graft-versus-host disease in pregnancy. As survival after stem cell transplant continues to improve, understanding the downstream consequences of the treatment, including for fertility and pregnancy, is of growing importance.
RESUMEN
OBJECTIVE: To study cycle outcomes of women who choose to pursue oocyte cryopreservation, using published age-specific oocyte recommendations DESIGN: Retrospective Cohort SUBJECTS: A total of 5,915 patients seeking planned oocyte cryopreservation, 3504 ultimately underwent ovarian stimulation with oocyte retrieval and cryopreservation, 425 of this cohort subsequently thawed with intent to utilize with embryo transfer EXPOSURE: Planned oocyte cryopreservation MAIN OUTCOME MEASURES: Planned oocyte cryopreservation consultation, fertility preservation cycle(s) and ovarian stimulation outcomes RESULTS: 5,915 women were seen in initial consultation for planned fertility preservation (2012-2022). Ethnicity and highest level of education were significant in predicting who would move forward with oocyte stimulation for fertility preservation. Women who reported working within law and public policy and in the fields of health and medicine were statistically more likely to proceed with a cycle than those who listed other occupations (p < 0.001). Of 3,504 women in the study cohort who underwent ovarian stimulation and egg retrieval, 1331 (38.0%) achieved the age-based recommended number of oocytes to freeze. Only 57 (4.3%) of these women who met their age-based oocyte goal did so following their initial cryopreservation cycle. There was a significant association between ethnicity and number of cryopreservation cycles, specifically showing that Black or African American women were less likely to complete two or more cycles (p < 0.001). Patients whose education background included graduate or professional degrees were more likely to have completed more than one cycle (p = 0.007). CONCLUSION: Self-identified ethnicity was significantly associated with the odds of moving forward with oocyte stimulation for fertility preservation and egg retrieval following initial consultation (p<0.001) with ethnic minorities significantly less likely to continue treatment. Of those who undergo egg freezing, most women pursue more than one stimulation and cryopreservation cycle, yet the majority never meet their recommended number to freeze.
RESUMEN
Introduction Medical indications for fertility preservation include any malignancy, chronic illness, or disease that would require gonadotoxic chemotherapy or radiation (conditioning regimens), which would impede a woman's ability to conceive in the future. Thus, any patient who plans to undergo a gonadotoxic regimen is advised to cryopreserve oocytes or embryos, which can be used in the future at the patient's convenience. Attempts have been made to suppress ovarian function with gonadotropin-releasing hormone agonists (GnRH-a) to induce ovarian quiescence and, thereby, theoretically limit the gonadotoxic impact on the follicular pool. We explored the use of leuprolide (a type of GnRH-a) in preventing primary ovarian insufficiency (POI) in a cohort study of patients who underwent hematopoietic stem cell transplants (HSCT) at the National Institutes of Health (NIH); since the conditioning regimens for HSCT include cyclophosphamide and other gonadotoxic therapies, we hypothesized that GnRH-a would be ineffective in preventing POI. Methods We assessed patients who underwent fertility preservation prior to their stem cell transplant, as their follicular-stimulating hormone (FSH) levels were evaluated prior to and post-chemotherapy. Twenty-nine patients who underwent hormonal evaluation prior to and post-chemotherapy were included. The control group did not receive GnRH-a prior to chemotherapy, while the treatment group did receive GnRH-a pre-chemotherapy. Results Our data revealed that 80% of the control group had menopausal levels post-chemotherapy, while 91% of the treatment group still had menopausal levels post-chemotherapy (p=0.33). Conclusions Thus, our hypothesis that GnRH-a is ineffective in reducing the risk of POI in a cohort of patients who receive conditioning regimens for HSCT was confirmed.
RESUMEN
Endometriosis is a debilitating gynecologic disorder characterized by chronic pelvic pain, pelvic adhesions and infertility. The gold standard diagnostic modality is histologically by tissue biopsy, although it can be diagnosed empirically if symptoms improve with medical treatment. A delayed diagnosis of endometriosis often leads to a significant impairment in quality of life and work productivity; hence, significant morbidity has been shown to bear a detrimental impact on society and the economy. The ongoing novel investigation into biomarkers for diagnostic or prognostic evaluation of endometriosis may aid in earlier detection, and thereby, improve patient quality-of-life as well as minimize morbidity. Currently, no single biomarker has been validated for endometriosis; however, there are emerging data on the utility of microRNA for diagnosis and prognosis of disease activity. In this brief review, we will identify and categorize the novel biomarkers for endometriosis.
RESUMEN
Objective: To evaluate the cost-effectiveness of in vitro fertilization with preimplantation genetic testing for monogenic disease (IVF + PGT-M) in the conception of a nonsickle cell disease (non-SCD) individual compared with standard of care treatment for a naturally conceived, sickle cell disease (SCD)-affected individual. Design: A Markov simulation model was constructed to evaluate a one-time IVF + PGT-M treatment compared with the lifetime standard of care costs of treatment for an individual potentially born with SCD. Using an annual discount rate of 3% for cost and outcome measures, quality-adjusted life years were constructed from utility weights and life expectancy values and then used as the effectiveness measurement. An incremental cost-effectiveness ratio was calculated for both treatment arms, and a willingness-to-pay threshold of $50,000 per quality-adjusted life year was assumed. Setting: Tertiary care or university medical center. Patients: A hypothetical cohort of 10,000 patients was analzyed over a lifetime horizon using yearly cycles. Interventions: In vitro fertilization with preimplantation genetic testing for monogenic disease use in conception of a non-SCD individual. Main Outcome Measures: The primary outcomes of interest were the incremental cost and effectiveness of an IVF+PGT-M conception compared with the SOC treatment of an SCD-affected individual. Results: In vitro fertilization with preimplantation genetic testing for monogenic disease was the optimal strategy in 93.17% of the iterations. An incremental savings of $137,594 was demonstrated with a gain of 1.96 QALYs and 3.69 life years over a lifetime. Sensitivity analysis demonstrated that SOC treatment never met equivalent cost-effectiveness. Conclusions: Our model demonstrates that IVF + PGT-M for selection against SCD, compared with lifetime SOC treatment for those affected, is the most cost-effective strategy within the United States healthcare sector.
RESUMEN
Since the first case of 17-alpha-hydroxylase-deficiency (17-OHD) was described in 1966, a number of cases have been reported with a clinical picture of hypertension, hypokalemia, and hypogonadism. Infertility is a major concern for some of these individuals. This mini-review aims to detail the components of this disorder that affect fertility and focus on the recent acceleration in the success of achieving live births, as well as highlight the unsuccessful attempts. The data supporting successful live births remains limited, but existing evidence suggests that in vitro fertilization can be used in conjunction with hormone replacement therapy and steroid suppression to achieve live birth in patients with infertility from 17-OHD.
RESUMEN
A receptive endometrium is required for successful embryo implantation. Endometrial thickness, as measured by ultrasonography, is the most commonly used marker of endometrial receptivity in assisted reproductive technology cycles. Several factors simultaneously affect both endometrial thickness and probability of live birth, including age, oestradiol concentration and oocyte number, among others. Most of the studies investigating a relationship between endometrial thickness and embryo transfer outcomes are retrospective and do not adequately address confounding factors, in addition to other limitations. Despite multiple meta-analyses and studies with large numbers of cycles, controversy still exists. The difference between the results from prospective and retrospective studies is also striking. This article presents a critical appraisal of the studies on endometrial thickness and embryo transfer outcomes in order to highlight methodological issues and how they can be overcome in future studies. Currently available evidence does not seem to support a modification of management just because endometrial thickness is below an arbitrary threshold.
Asunto(s)
Implantación del Embrión , Transferencia de Embrión , Humanos , Embarazo , Femenino , Estudios Retrospectivos , Estudios Prospectivos , Transferencia de Embrión/métodos , Técnicas Reproductivas Asistidas , Endometrio/diagnóstico por imagen , Índice de EmbarazoAsunto(s)
Infertilidad Femenina , Infertilidad , Neoplasias , Humanos , Femenino , Incidencia , Infertilidad/diagnóstico , Infertilidad/epidemiología , Infertilidad/terapia , Neoplasias/epidemiología , Neoplasias/complicaciones , Infertilidad Femenina/diagnóstico , Infertilidad Femenina/epidemiología , Infertilidad Femenina/terapiaRESUMEN
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.
Asunto(s)
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
In patients with varying hematologic disorders (thalassemia, sickle cell anemia, aplastic anemia, etc.), inherited bone marrow failure syndromes, and immune deficiencies due to a single gene disorder, the advent of stem cell transplantation (SCT) as a treatment option has allowed for significant disease improvement, and possibly cure. This specific treatment option often requires exposure to chemotherapeutic agents and sometimes whole body radiation; therefore, primary ovarian insufficiency is often sequelae of the therapy. The optimization of fertility preservation protocols within this patient population is of extreme importance. This review aims to detail the use of GnRH agonist use within this patient population, within the context of fertility preservation cycles.
Asunto(s)
Preservación de la Fertilidad , Enfermedades Genéticas Congénitas , Hormona Liberadora de Gonadotropina , Fertilización In Vitro , Hormona Liberadora de Gonadotropina/agonistas , Humanos , Inducción de la Ovulación/métodosRESUMEN
Endometrial health is affected by molecular processes that underlie estrogen responses. We assessed estrogen regulation of endometrial function by integrating the estrogen receptor α (ESR1) cistromes and transcriptomes of endometrial biopsies taken from the proliferative and mid-secretory phases of the menstrual cycle together with hormonally stimulated endometrial epithelial organoids. The cycle stage-specific ESR1 binding sites were determined by chromatin immunoprecipitation and next-generation sequencing and then integrated with changes in gene expression from RNA sequencing data to infer candidate ESR1 targets in normal endometrium. Genes with ESR1 binding in whole endometrium were enriched for chromatin modification and regulation of cell proliferation. The distribution of ESR1 binding sites in organoids was more distal from gene promoters when compared to primary endometrium and was more similar to the proliferative than the mid-secretory phase ESR1 cistrome. Inferred organoid estrogen/ESR1 candidate target genes affected formation of cellular protrusions and chromatin modification. Comparison of signaling effected by candidate ESR1 target genes in endometrium vs organoids reveals enrichment of both overlapping and distinct responses. Our analysis of the ESR1 cistromes and transcriptomes from endometrium and organoids provides important resources for understanding how estrogen affects endometrial health and function.
Asunto(s)
Receptor alfa de Estrógeno , Organoides , Cromatina/genética , Cromatina/metabolismo , Endometrio/metabolismo , Receptor alfa de Estrógeno/metabolismo , Estrógenos/metabolismo , Femenino , Humanos , Ciclo Menstrual/fisiología , Organoides/metabolismoRESUMEN
Steroid-producing cells contain key cytochrome P450 enzymes, such as side-chain cleavage (P450-SCC) and 17α-hydroxylase (17α-OH). They are required for steroid hormone synthesis and considered antigens associated with Addison's disease and autoimmune primary ovarian insufficiency (POI). We studied an animal model for human autoimmune POI in mice with autoimmune oophoritis induced by neonatal thymectomy performed at day 3 (TX3). We previously identified an oocyte-specific protein as a major antigen inciting autoimmune oophoritis in mice. In this study, we characterized ovarian steroid-producing cell antigens. Using indirect immunofluorescence staining, we tested immune reactions in mouse ovarian and adrenal tissue sections with sera from TX3 female mice. More than half of the TX3 mice (8 of 15) produced antibodies reacting with both ovarian and adrenal steroid-producing cells, including some that reacted to oocytes as well. We produced recombinant proteins for the three key steroidogenic enzymes 17α-OH, P450-SSC, and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and tested their immune reactions with individual mouse sera. By immunoblotting, all mouse sera that reacted with the steroid-producing cells (n = 8) were shown to react with the P450-SCC, but not with the 17α-OH or 3ß-HSD recombinant proteins. The sham-operated mouse sera and TX3 mouse sera negative for steroid-producing cells did not react with the P450-SCC recombinant protein. Our findings indicate that the P450-SCC is a specific and unique major antigen within the ovarian steroid-producing cells. Given their similarity of predicted antigenicity, we assume that P450-SCC acts in human autoimmune POI as it does in mouse autoimmune oophoritis.
Asunto(s)
Enfermedad de Addison , Insuficiencia Ovárica Primaria , Animales , Autoantígenos , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol , Femenino , Humanos , Ratones , Ooforitis , Poliendocrinopatías Autoinmunes , Proteínas Recombinantes , Esteroide 17-alfa-Hidroxilasa , EsteroidesRESUMEN
Objective: To examine the relationship of preconception hemoglobin A1c, a marker of cumulative exposure to glucose over the preceding 2-3 months, with time to pregnancy, pregnancy loss, and live birth among fecund women without diagnosed diabetes or other medical diseases. Design: A secondary analysis of a prospective cohort of women participating in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial. Setting: Four US academic medical centers. Patients: A total of 1,194 healthy women aged 18-40 years with a history of one or two pregnancy losses attempting spontaneous conception were observed for up to six cycles while attempting pregnancy and throughout pregnancy if they conceived. Interventions: Not applicable. Main Outcome Measures: Time to pregnancy, human chorionic gonadotropin pregnancy, clinical pregnancy, pregnancy loss, and live birth. Results: Although increasing preconception A1c level was associated with reduced fecundability (fecundability odds ratio [FOR] per unit increase in A1c 0.74; 95% confidence interval [CI] 0.57, 0.96) in unadjusted models and models adjusted for age, race, smoking and treatment arm (FOR 0.79; 95% CI 0.60, 1.04), results were attenuated after further adjustment for body mass index (FOR 0.91; 95% CI 0.68, 1.21). Preconception A1c levels among women without diagnosed diabetes were not associated with live birth or pregnancy loss. Conclusionss: Among healthy women without diagnosed diabetes, we observed no association of A1c with live birth or pregnancy loss. The association between A1c and fecundability was influenced by body mass index, a strong risk factor for both diabetes and infertility. These data support current recommendations that preconception A1c screening should be reserved for patients with risk factors for diabetes. Clinical Trial Registration Number: ClinicalTrials.gov: NCT00467363.
RESUMEN
Since the advent of ART, technology has continuously evolved to improve embryology and pregnancy outcomes. However, not all technologies that are integrated into practice have convincing evidence of clinical effectiveness, and they often increase the financial burden of fertility care. We discuss here a selection of commonly utilized IVF "add-ons" and discuss the existing evidence for their utility. The procedures included in this review are time-lapse imaging of embryos, assisted hatching, EmbryoGlue, sperm DNA testing, egg activation with calcium ionophore, endometrial receptivity array, and physiological intracytoplasmic sperm injection (PICSI). While there is rather limited supporting evidence for nearly all IVF add-ons that we reviewed, there is strong demand from patients, physicians, and the biotechnology industry to continue further research and development in this arena. We propose that all add-on procedures should provide true efficacy for the patient, and reproductive endocrinologists should inform patients of the costs and benefits of utilizing various technologies before they undergo treatment. In the future, add-ons that show clear evidence of efficacy and justifiable cost should be incorporated into routine practice, while others that do not meet these criteria should be phased out entirely.
Asunto(s)
Fertilización In Vitro , Nacimiento Vivo , Endometrio , Femenino , Fertilización In Vitro/métodos , Humanos , Embarazo , Índice de Embarazo , Inyecciones de Esperma Intracitoplasmáticas , Resultado del TratamientoRESUMEN
OBJECTIVE: This study aimed to examine whether prenatal low-dose aspirin (LDA) therapy affects risk of cesarean versus vaginal delivery. STUDY DESIGN: This study is a secondary analysis of the randomized clinical effects of aspirin in gestation and reproduction (EAGeR) trial. Women received 81-mg daily aspirin or placebo from preconception to 36 weeks of gestation. Mode of delivery and obstetric complications were abstracted from records. Log-binomial regression models estimated relative risk (RR) of cesarean versus vaginal delivery. Data were analyzed among the total preconception cohort, as well as restricted to women who had a live birth. RESULTS: Among 1,228 women, 597 had a live birth. In the intent-to-treat analysis, preconception-initiated LDA was not associated with risk of cesarean (RR = 1.02; 95% confidence interval [CI]: 0.98-1.07) compared with placebo. Findings were similar in just women with a live birth and when accounting prior cesarean delivery and parity. CONCLUSION: Preconception-initiated daily LDA was not associated with mode of delivery among women with one to two prior losses. KEY POINTS: · Aspirin was not associated with risk of cesarean section.. · Aspirin was not associated with mode of delivery.. · No increased risk of bleeding with use of aspirin..