High ovarian responders have the highest risk of premature progesterone rise.

OBJECTIVE: Late follicular phase progesterone elevation is a complication that affects approximately 38% of IVF cycles. There is a lack of consensus on the appropriate cut-off levels for progesterone on hCG day. Although premature progesterone rise occurs in all kinds of ovarian responses, there is a knowledge gap regarding the ovarian response with the highest risk of this phenomenon. Our study aims to assess the relative risk of each kind of ovarian response for premature progesterone rise and evaluate the prevalence of premature progesterone rise in each ovarian response. METHODS: A retrospective, cross-sectional, comparative and analytic study was performed at the Reproductive Endocrinology Department in Centro Médico Nacional 20 de Noviembre in Mexico City. All conventional-antagonist cycles were grouped according to their ovarian response and were evaluated from 2015 to 2020. Pearson's Squared-chi, Cramer's V, cross-table and the relative risk were calculated. RESULTS: The prevalence of premature progesterone rise oscillated from 20.8 to 67.9% for low and high ovarian responders, respectively. After calculating the relative risk, high ovarian responders had a 1.38 higher risk for premature progesterone rise than other groups. CONCLUSIONS: High ovarian responders have the highest risk for premature progesterone rise compared to normal and low ovarian responders. High ovarian responders have a 67.9% prevalence of premature progesterone rise.

Iatrogenic and demographic determinants of the national plural birth increase.

OBJECTIVE: To study the contribution of ovulation induction and ovarian stimulation, in vitro fertilization (IVF), and unassisted conception to the increase in national plural births in the United States, a significant contributor to adverse maternal and infant health outcomes. DESIGN: National and IVF-assisted plural birth data were derived from the Centers for Disease Control and Prevention's National Vital Statistics System (1967-2021, after introduction of Clomiphene Citrate in the United States) and the National Assisted Reproductive Technology Surveillance System (1997-2021), respectively. SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): In addition to IVF-assisted plural births, the contributions of unassisted conception to plural births among women aged <35 and ≥35 years were estimated using plural birth rates from 1949-1966 and a Bayesian logistic model with race and age as independent variables. The contribution of ovulation induction and ovarian stimulation was estimated as the difference between national plural births and IVF-assisted and unassisted counterparts. RESULT(S): From 1967-2021, the national twin birth rate increased 1.7-fold to a 2014 high (33.9/1,000 live births), then declined to 31.2/1,000 live births; the triplet and higher order birth rate increased 6.7-fold to a 1998 high (1.9/1,000 live births), then declined to 0.8/1,000 live births. In 2021, the contribution of unassisted conception among women aged <35 years to the national plural births was 56.1%, followed by ovulation induction and ovarian stimulation (19.5%), unassisted conception among women aged ≥35 years (16.8%), and IVF (7.6%). During 2009-2021, the contribution of ovulation induction and ovarian stimulation has remained stable, the contribution of unassisted conception among women aged <35 and ≥35 years has increased, and the contribution of IVF has decreased. CONCLUSION(S): Ovulation induction and ovarian stimulation are leading iatrogenic contributors to plural births. They are, therefore, targets for intervention to reduce the adverse maternal and infant health outcomes associated with plural births. Maternal age of ≥35 years is a significant contributor to the national plural birth increase.

Association of serum uric acid with women's ovarian reserve: observational study and Mendelian randomization analyses.

OBJECTIVE: To investigate the association between serum uric acid and women's ovarian reserve. DESIGN: Retrospective observational study and Mendelian randomization study. SETTING: University-affiliated in vitro fertilization center. PATIENTS: Observational analyses were undertaken using data from 8,257 women with infertility who finished their first in vitro fertilization treatments between May 2017 and December 2021. Mendelian randomization analyses were based on genome-wide association summary statistics from several biobanks of predominantly European ancestries. INTERVENTIONS: Observational study involved testing log2 transformed serum uric acid levels (for linear, negative regression, and logistic regression analyses); original uric acid levels (for nonlinear association analyses). Mendelian randomization study involved testing genetically predicted uric acid levels. MAIN OUTCOME MEASURES: Biomarkers including antimüllerian hormone, basal antral follicle count, follicle-stimulating hormone, luteinizing hormone, ratio of follicle-stimulating hormone to luteinizing hormone, estradiol; indices of ovarian response to stimulation including poor ovarian response according to different criteria and oocyte yield. RESULTS: In retrospective observational study, all ovarian reserve-related outcomes demonstrated significant differences across serum uric acid quartiles. A two-fold uric acid increase was associated with increased antimüllerian hormone (adjusted ß = 0.69; 95% confidence interval [CI], 0.43-0.95), antral follicle count (adjusted incidence rate ratio = 1.10, 95% CI, 1.05-1.14), luteinizing hormone (adjusted ß = 0.53, 95% CI, 0.28-0.78), decreased risks of Bologna poor ovarian response (adjusted odds ratio = 0.97; 95% CI, 0.95-0.99) and groups 2-4 Poseidon poor ovarian response (group 2: 0.63, 0.56-0.71; group 3: 0.71, 0.65-0.78; group 4: 0.50, 0.46-0.55), whereas an increased risk of group 1 (1.26, 1.13-1.41). Nonlinear analyses showed a common inflection point at 320-340 µmol/L of uric acid. Interactions between uric acid and antimüllerian hormone and antral follicle count were presented in association with oocyte yield. Mendelian randomization results suggested a significant association between genetically predicted uric acid levels and antimüllerian hormone levels (ß = 0.08; 95% CI, 0.04-0.12) but none for uric acid in relation to polycystic ovarian syndrome or other related hormones. CONCLUSION: Higher uric acid levels were associated with better ovarian reserve and increased levels of antimüllerian hormone albeit an increased risk of unexpected poor ovarian response.

Valor preditivo do volume ovariano na resposta à induçäo da ovulaçäo na fertilizaçäo in vitro / predictive value of ovarian volume in the response to in vitro fertilization

Determinar a correlaçäo entre o volume ovariano medido pela ultra-sonografia transvaginal (USTV) com o cancelamento da induçäo da ovulaçäo nos ciclos de fertilizaçäo in vitro (FIV) devido à má resposta. Estudamos a resposta de 117 pacientes submetidas a induçäo da ovulaçäo para FIV. As pacientes foram divididas em dois grupos: Grupo I = volume ovariano < 3cm cubicos e Grupo II = volume ovariano >ò 3cm cubicos. As pacientes do grupo I obtiveram uma maior taxa de cancelamento da induçäo da ovulaçäo devido a má resposta (52 por cento) que as pacientes do grupo II (21 por cento) (p<0,001). As pacientes do grupo I tiveram menor número de folículos recrutados (4,66) que a do grupo II (9,5) (P<0,01). Näo houve diferença estatisticamente significativa entre idade, número de dias de induçäo da ovulaçäo e número de ampolas de gonadotrofinas utilizadas. Nossos resultados sugerem uma importante associaçäo da reserva ovariana com o volume ovariano. Os ovários com dimensöes < 3cm cubicos de volume estäo associados ao maior índice de cancelamento da induçäo da ovulaçäo devido à má resposta.

¿Qué resultados se pueden esperar de la técnica fertilización in vitro y de otras técnicas de fertilización asistida? / What results could we hope about in vitro fertilization and other assisted fertilization technics

Los resultados de la FIV-TU, GIFT y ZIFT han mejorado progresivamente en los últimos años pero aún distan de ser satisfactorios especialmente cuando son analizados en términos de costo-eficiencia. Durante 1990, en la literatura mundial, se comunicaron resultados de aproximadamente 20% de embarazos y 15% de partos en casos de FIV-TU, 29% de embarazos y 22% de partos en GIFT y 21% de embarazos y 16% de partos en ZIFT. Los resultados en Chile, pese al pequeño número de casos informados en publicaciones, son aparentemente similares a los de USA y Europa. Los éxitos en fertilización asistida han aumentado con el uso de análogos Gn-RH y disminuyen en pacientes mayores de 35 años de edad. Las tasas de embarazos son más elevadas cuando aumenta el número de ovocitos o de embriones transferidos. Sin embargo, la transferencia de más de 3 ó 4 ovocitos o embriones se ha contraindicado por los riesgos de los embarazos múltiples especialmente en los triples o mayores. Cuando, por fertilización "in vitro", se obtiene un alto número de embriones es frecuente que se recurra a su congelación para transferirlos en ciclos posteriores. La FIV-TU es la alternativa primaria de tratamiento cuando existe daño tubo-peritoneal severo evidenciado por la existencia de adherencias extensas y densas, por hidrosálpinx grandes con paredes gruesas y componente inflamatorio importante o por obstrucción con fibrosis de ambas trompas. En los casos en que la microcirugía tubo-ovárica no da resultados después de un año de la intervención se recomienda la FIV-TU. Cuando las trompas son sanas, las inseminaciones intrauterinas en 3 ó 4 ciclos de hiperestimulación ovárica controlada con gonadotrofinas, dan tasas de embarazos que se aproximan a las que se obtienen con procedimientos de fertilización asistida. La complicación más rigurosa de la fertilización asistida, además de los embarazos múltiples, es el síndrome de hiperestimulación ovárica severa. Este se previene absteniéndose de administrar HCG o de efectuar la transferencia de óvulos o embriones en casos de valores elevados de estradiol plasmático después de la administración de FSH y/o HMG

Inducción de ovulación: II pacientes clomifeno negativas

En pacientes que no responden a la terapia con citrato de clomifeno, se utiliza un protocolo basado en dosis bajas de clomifeno y gonadotrofina menopáusica humana (HMG). Se obtiene 51.2 por ciento de ovulación en 35 ciclos. Las pacientes obesas tienen una baja respuesta al esquema de inducción de ovulación lo mismo que las pacientes con una relación LH/FSH mayor de 2.68. No se presentan síntomas de hiperestimulación ovárica. En las pacientes que ovulan se utiliza 50 mg/día por 5 dosis de clomifeno y un promedio de 2.2 ampollas de 75 UI de HMG por ciclo en promedio. El promedio del tamaño del folículo al momento de ovulación es de 18.66 +o- 4.9mm. El 60 por ciento de las pacientes ovulan 24-48 horas posterior a la aplicación de HCG; restante lo hacen a las 24 horas o menos. Se discute la utilidad y las indicaciones de protocolos alternos en pacientes "resistentes" al clomifeno