RESUMEN
Introduction: This study compared, in high responders undergoing IVF treatment, GnRH agonist-only trigger and dual trigger on oocyte retrieval rate and cumulative live birth rate (LBR). The aim was to determine if the GnRH agonist-only triggers had provided outcomes comparable to dual trigger, while minimizing the risk of ovarian hyperstimulation syndrome (OHSS). Materials and methods: A retrospective, matched case-control study was conducted at Taichung Veterans General Hospital, Taiwan, including women who underwent IVF/ICSI between January 1, 2014, and December 31, 2022. Inclusion criteria were: GnRH antagonist protocol and estrogen level >3,000 pg/ml on trigger day. Exclusion criteria were: immune/metabolic diseases, donated oocytes, and mixed stimulation cycles. Propensity score matching was applied to balance age, AMH level, and oocyte number between the GnRH agonist-only and dual trigger groups. Outcomes were analyzed for patients who had complete treatment cycles, focusing on oocyte retrieval rate and cumulative LBR. Results: We analyzed 116 cycles in the agonist-only group, and 232 cycles in the dual trigger group. No inter-group difference was found in their age, BMI, and AMH levels. The dual trigger group had a higher oocyte retrieval rate (93% vs. 80%; p <0.05), while fertilization rates, blastocyst formation rates, and cumulative LBR were comparable. Notably, no OHSS cases had been reported in the GnRH agonist-only group, compared with 7 cases in the dual trigger group. Conclusion: GnRH agonist-only triggers resulted in a lower oocyte retrieval rate compared to dual triggers but did not significantly affect cumulative LBR in high responders. This approach effectively reduces OHSS risk without compromising pregnancy outcomes, making it a preferable option in freeze-all strategies, despite a longer oocyte pick-up duration and a medium cost. GnRH agonist-only trigger, however, may not be suitable for fresh embryo transfers or patients with low serum LH levels on trigger day.
Asunto(s)
Tasa de Natalidad , Fertilización In Vitro , Hormona Liberadora de Gonadotropina , Recuperación del Oocito , Síndrome de Hiperestimulación Ovárica , Inducción de la Ovulación , Humanos , Femenino , Hormona Liberadora de Gonadotropina/agonistas , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Adulto , Recuperación del Oocito/métodos , Inducción de la Ovulación/métodos , Estudios Retrospectivos , Embarazo , Estudios de Casos y Controles , Fertilización In Vitro/métodos , Síndrome de Hiperestimulación Ovárica/prevención & control , Síndrome de Hiperestimulación Ovárica/epidemiología , Nacimiento Vivo/epidemiología , Índice de Embarazo , Fármacos para la Fertilidad Femenina/uso terapéutico , Fármacos para la Fertilidad Femenina/administración & dosificación , Taiwán/epidemiología , Inyecciones de Esperma Intracitoplasmáticas/métodosRESUMEN
BACKGROUND: Overweight women undergoing IVF treatment have lower success rates. Letrozole, an aromatase inhibitor, has been used as an adjunct for IVF treatment, but its specific effects in overweight women have not been investigated. This study was to explore the effects of letrozole co-treatment in an antagonist protocol for overweight infertile women undergoing IVF treatment. METHODS: This retrospective cohort study included overweight infertile women who underwent IVF/ICSI treatment and fresh embryo transfer (ET), with or without letrozole co-treatment in an antagonist protocol, from 2007 to 2021 at Shanghai Ninth People's Hospital (Shanghai, China). A total of 704 overweight infertile women were included: 585 women were in the antagonist group, and 119 women were in the letrozole co-treatment group. The primary outcome was the live birth rate after fresh ET. Propensity score-based patient-matching was employed to balance the covariates between the groups. Multivariate logistic regression analysis was also performed to estimate odds ratio (OR) and 95% confidence interval (CI) for association of letrozole co-treatment and the live birth outcome. RESULTS: Letrozole co-treatment induced significant changes in hormonal profile on the trigger day. The letrozole group exhibited a decrease in the total number of follicles compared to the antagonist group, but a higher proportion of large follicles at oocyte retrieval (P < 0.05). The quantity and quality of embryos were comparable between the two groups (P > 0.05). The letrozole co-treatment group had a significantly higher live birth rate than the control group (38.7% vs. 22.6%, P = 0.026). With multivariate logistic regression analysis, letrozole co-treatment was associated with higher odds of live birth after adjusting for potential confounding factors (adjusted OR = 2.00, 95% CI = 1.17-3.39, P = 0.011). Letrozole presented no significant associations with obstetrical or neonatal complications (P > 0.05). CONCLUSION: Letrozole co-treatment in an antagonist protocol may offer potential benefits for overweight infertile women undergoing IVF treatment. Further research is warranted to validate these findings and explore the broader implications for letrozole co-treatment.
Asunto(s)
Inhibidores de la Aromatasa , Transferencia de Embrión , Fertilización In Vitro , Infertilidad Femenina , Letrozol , Sobrepeso , Índice de Embarazo , Humanos , Letrozol/uso terapéutico , Femenino , Estudios Retrospectivos , Adulto , Embarazo , Inhibidores de la Aromatasa/uso terapéutico , Fertilización In Vitro/métodos , Infertilidad Femenina/terapia , Transferencia de Embrión/métodos , Inducción de la Ovulación/métodos , Nacimiento Vivo , China , Inyecciones de Esperma IntracitoplasmáticasRESUMEN
OBJECTIVE: This study aimed to evaluate the impact of adding 4 mg estradiol valerate to progesterone for luteal support on pregnancy rates in IVF cycles following a long protocol with reduced luteal serum estradiol levels post-hCG triggering. DESIGN, SETTING, AND PARTICIPANTS: The prospective randomized controlled trial was conducted at a public tertiary hospital reproductive center with 241 patients who experienced a significant decrease in serum estrogen levels post-oocyte retrieval. INTERVENTIONS: Participants received either a daily 4 mg dose of estradiol valerate in addition to standard progesterone or standard progesterone alone for luteal support. RESULTS: The ongoing pregnancy rate did not show a significant difference between the E2 group and the control group (56.6% vs. 52.2%, with an absolute rate difference (RD) of 4.4%, 95% CI -0.087 to 0.179, P = 0.262). Similarly, the live birth rate, implantation rate, clinical pregnancy rate, early abortion rate, and severe OHSS rate were comparable between the two groups. Notably, the E2 group had no biochemical miscarriages, contrasting significantly with the control group (0.0% vs. 10.7%, RD -10.7%, 95% CI -0.178 to -0.041, P = 0.000). In the blastocyst stage category, the clinical pregnancy rate was notably higher in the E2 group compared to the control group (75.6% vs. 60.8%, RD 14.9%, 95% CI 0.012 to 0.294, P = 0.016). CONCLUSION: Adding 4 mg estradiol valerate to progesterone for luteal support does not affect the ongoing pregnancy rate in embryo transfer cycles using a long protocol with a significant decrease in serum estradiol levels after hCG triggering. However, it may reduce biochemical miscarriages and positively impact clinical pregnancy rates in blastocyst embryo transfer cycles. TRIAL REGISTRATION: ChiCTR1800020342.
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Gonadotropina Coriónica , Estradiol , Fertilización In Vitro , Fase Luteínica , Inducción de la Ovulación , Índice de Embarazo , Progesterona , Humanos , Femenino , Estradiol/sangre , Estradiol/administración & dosificación , Embarazo , Adulto , Gonadotropina Coriónica/administración & dosificación , Fase Luteínica/efectos de los fármacos , Fase Luteínica/sangre , Fertilización In Vitro/métodos , Progesterona/sangre , Progesterona/administración & dosificación , Estudios Prospectivos , Inducción de la Ovulación/métodos , Transferencia de Embrión/métodos , Recuperación del Oocito/métodosRESUMEN
BACKGROUND: Managing infertility patients with poor ovarian response (POR) to ovarian stimulation remains unmet clinically. Besides economic burdens, patients with POR have a poor prognosis during in vitro fertilization and embryo transfer (IVF-ET). In this study, we assessed the efficacy and safety of Shen Que (RN8) moxibustion on reproductive outcomes in POSEIDON patients (Group 2a). METHODS: Women eligible for IVF were invited to participate in this randomized, open-label, superiority trial at an academic fertility center from January 2022 to December 2023. One hundred patients ≤ 44 years old equally divided between Shen Que moxibustion (SQM) and control groups were randomized. These patients must meet the POSEIDON criteria, Group 2a, which requires antral follicle count (AFC) ≥ 5 or anti-müllerian hormone (AMH) ≥ 1.2ng/ml, and a previous unexpected POR (< 4 oocytes). Twelve moxibustion sessions were conducted in the SQM group prior to oocyte retrieval, while only IVF treatment was performed in the control group. The primary outcome was the number of oocytes retrieved. RESULTS: As compared with the IVF treatment alone, the SQM + IVF treatment significantly increased the number of retrieved oocytes (4.7 vs. 5.8, p = 0.012), mature oocytes (3.0 vs. 5.0, p = 0.008), and available embryos (2.0 vs. 4.0, p = 0.014) in unexpected poor ovarian responders aged more than 35 years. In the SQM group, the cumulative live birth rate was 27.3% (9/33) in comparison to 13.3% (4/30) in the control group, whereas no statistical significance was detected (p = 0.172). During the study, no significant adverse effects were observed. CONCLUSIONS: Women with unexpected POR who meet POSEIDON Group 2a can benefit from Shen Que (RN8) moxibustion treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05653557.
Asunto(s)
Fertilización In Vitro , Moxibustión , Inducción de la Ovulación , Humanos , Femenino , Moxibustión/métodos , Adulto , Inducción de la Ovulación/métodos , Embarazo , Fertilización In Vitro/métodos , Recuperación del Oocito/métodos , Transferencia de Embrión/métodos , Resultado del Tratamiento , Infertilidad Femenina/terapia , Índice de EmbarazoRESUMEN
PURPOSE: This study aimed to examine the correlation between different dominant follicle proportions (DFPs) and outcomes of in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) among patients classified under POSEIDON Groups 3 and 4, who underwent gonadotropin-releasing hormone antagonist (GnRH-ant) protocols. Additionally, it sought to determine the optimal DFP threshold for trigger timing. METHODS: A retrospective analysis was performed on patients classified under POSEIDON Groups 3 (n = 593) and 4 (n = 563) who underwent GnRH-ant protocols for controlled ovarian hyperstimulation (COH) between 2016 and 2022. These patients were categorized into two groups based on their DFPs, defined as the ratio of ≥ 18-mm dominant follicles to ≥ 12-mm follicles on the trigger day (DFP ≤ 40% and DFP ≥ 40%). Statistical analyses, including restricted cubic spline (RCS) and multivariate logistic regression, were employed to assess the relationship between DFP and IVF/ICSI outcomes. RESULTS: Demographic characteristics of patients were similar across groups. In POSEIDON Groups 3 and 4, DFP > 40 was associated with a significant decrease in the number (No.) of oocytes retrieved, cleaved embryos, and available embryos. Moreover, following the GnRH-ant cycle, the clinical pregnancy and live birth rates in fresh embryo transfer (ET) were notably reduced in the DFP > 40 group compared with the DFP ≤ 40 group, whereas no significant differences were observed in the pregnancy outcomes of the first frozen-thawed embryo transfer (FET) between the groups. In POSEIDON Group 3, the cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLRB) were significantly higher in the DFP ≤ 40 subgroup than in the DFP > 40 subgroup, with a notable decrease in CLRB observed with increasing DFP levels. However, in POSEIDON Group 4, no significant differences in CCPR and CLRB were found between the groups. Logistic regression analysis identified age and the No. of oocytes retrieved as pivotal factors influencing CLRB in Group 4. CONCLUSION: For patients in POSEIDON Group 3, maintaining a DFP ≤ 40 mm is crucial to achieve optimal laboratory and pregnancy outcomes by avoiding delayed triggering. However, for patients in POSEIDON Group 4, age remains a critical factor influencing CLRB regardless of DFP, although a higher No. of oocytes retrieved and available embryos with DFP ≤ 40 is beneficial.
Asunto(s)
Fertilización In Vitro , Hormona Liberadora de Gonadotropina , Folículo Ovárico , Inducción de la Ovulación , Inyecciones de Esperma Intracitoplasmáticas , Humanos , Femenino , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Estudios Retrospectivos , Adulto , Inyecciones de Esperma Intracitoplasmáticas/métodos , Embarazo , Fertilización In Vitro/métodos , Folículo Ovárico/efectos de los fármacos , Inducción de la Ovulación/métodos , Índice de Embarazo , Pronóstico , Antagonistas de Hormonas/uso terapéutico , Resultado del EmbarazoRESUMEN
BACKGROUND: Insulin resistance (IR) is related with adverse outcomes of in vitro fertilization (IVF) in women with obesity, but little is known about the relationship between IR and unexpected poor ovarian response (uPOR) in non-obese subjects with sufficient ovarian parameters (classified as POSEIDON group 1). This research aims to explore the association between the homeostasis model assessment of insulin resistance (HOMA-IR) and uPOR in non-obese women with normal biomarkers of ovarian reserve. METHODS: The retrospective cohort study was conducted at a fertility center. The main inclusion criteria were age < 35 years, body mass index (BMI) < 28 kg/m2, normal ovarian reserve (anti-Mullerian hormone ≥ 1.2 ng/ml, antral follicle count ≥ 5). Women undergoing the first oocyte retrieval cycle were included consecutively between 2018 until 2023. Patients who have ≤ 9 oocytes retrieved were defined as uPOR. The multivariable logistic model and subgroup analysis were conducted after adjusting confounders. RESULTS: A total of 6977 cycles were included. The adjusted odds ratio was 1.25 (95% confidence interval [CI], 1.12-1.39) for the increment of Ln HOMA-IR which was taken as a continuous variable. Meanwhile, as a sensitivity analysis, elevated tertile of HOMA-IR exhibited an increase in risk of uPOR for the third tertile (≥ 2.75) when compared with the first tertile (< 1.75) with OR of 1.33 (95%CI, 1.15-1.54). In the subgroup analysis, the positive association remained consistent. CONCLUSION: Elevated HOMA-IR values is significantly associated with increased risk of uPOR in non-obese women classified as POSEIDON group 1. Our study provided evidence for the adverse influence of IR on the ovarian response during IVF and shed light on the importance of IR measurement at the time of pre-stimulation among non-obese women.
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Fertilización In Vitro , Resistencia a la Insulina , Humanos , Femenino , Estudios Retrospectivos , Adulto , Inducción de la Ovulación , Reserva Ovárica , Índice de Masa Corporal , Recuperación del Oocito , Ovario , Obesidad/sangreRESUMEN
Objective: To exlplore the association between the baseline luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio of polycystic ovary syndrome (PCOS) and in vitro fertilisation-embryo transfer outcomes. Methods: This was a retrospective cohort study. A total of 2 868 PCOS patients were enrolled, all of the participants were patients in The First Affiliated Hospital of Anhui Medical University Hospital from October 2015 to October 2021. Propensity score matching (1â¶2.5) was conducted to regulate the non-random allocation of patients. Data were extracted from the hospital's medical records. Patients with baseline LH/FSH ratio>2 were deemed as study group, patients with baseline LH/FSH ratio≤2 were deemed as control group. Single factor analysis was applied to compare the differences of pregnancy outcomes between two groups. Results: After propensity score matching (1â¶2.5), there were no statistically significant differences in baseline data between the two groups (all P>0.05), indicating that the data were comparable. In the study group, the total dose of gonadotropin (Gn) and duration of Gn were lower than those of the control group (t=4.989, P<0.001; t=3.267, P=0.001), the rate of in vitro maturation was higher than that of the control group (χ2=4.938, P=0.026), the number of retrieved oocytes and cleavage were higher than those of the control group (t=-2.305, P=0.021; t=-2.816, P=0.005), but there were no differences in the number and rate of high-quality embryos between the two groups (t=-1.636, P=0.102; t=-0.123, P=0.902). The incidence of moderate to severe ovarian hyperstimulation syndrome in the study group was significantly higher than that in the control group (χ2=17.277, P<0.001). Regardless of fresh embryo transfer or frozen-thawed embryo transfer cycles, the incidences of gestational diabetes mellitus in the study group were higher than those in the control group (χ2=9.174, P=0.002; χ2=4.204, P=0.040) of singleton pregnancy. In the fresh embryo transfer cycle, the clinical pregnancy rate [30.30% (20/66) vs 47.75% (53/111)] and delivery rate [30.30% (20/66) vs 46.85% (52/111)] in the study group were lower than those in the control group (χ2=5.198, P=0.023; χ2=4.695, P=0.030). In the frozen-thawed embryo transfer cycle, the delivery rate in the study group was higer than that in the control group [59.41% (423/712) vs 55.04% (1 053/1 913); χ2=7.526, P=0.023]. The clinical pregnancy rate and delivery rate of fresh embryo transfer cycle in the study group were significantly lower than those of frozen-thawed embryo transfer cycle (χ2=21.308, P<0.001; χ2=20.871, P<0.001), but there were no significant differences in the control group (all P>0.05). Conclusions: PCOS patients with a higher basal LH/FSH ratio are more likely to develop moderate to severe ovarian hyperstimulation syndrome after controlled ovarian stimulation and have a higher incidence of gestational diabetes mellitus. Better pregnancy outcome could be obtained by frozen-thawed embryo transfer.
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Transferencia de Embrión , Fertilización In Vitro , Síndrome del Ovario Poliquístico , Índice de Embarazo , Adulto , Femenino , Humanos , Embarazo , Transferencia de Embrión/métodos , Fertilización In Vitro/métodos , Hormona Folículo Estimulante/sangre , Infertilidad Femenina/terapia , Infertilidad Femenina/etiología , Hormona Luteinizante/sangre , Síndrome de Hiperestimulación Ovárica/etiología , Síndrome de Hiperestimulación Ovárica/epidemiología , Inducción de la Ovulación/métodos , Síndrome del Ovario Poliquístico/terapia , Resultado del Embarazo , Puntaje de Propensión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: To quantitatively evaluate the effect of coenzyme Q10 (CoQ10) pretreatment on outcomes of IVF or ICSI in women with diminished ovarian reserve (DOR) based on the existing randomized controlled trials (RCTs). METHODS: Nine databases were comprehensively searched from database inception to November 01, 2023, to identify eligible RCTs. Reproductive outcomes of interest consisted of three primary outcomes and six secondary outcomes. The sensitivity analysis was adopted to verify the robustness of pooled results. RESULTS: There were six RCTs in total, which collectively involved 1529 participants with DOR receiving infertility treatment with IVF/ICSI. The review of available evidence suggested that CoQ10 pretreatment was significantly correlated with elevated clinical pregnancy rate (OR = 1.84, 95%CI [1.33, 2.53], p = 0.0002), number of optimal embryos (OR = 0.59, 95%CI [0.21, 0.96], p = 0.002), number of oocytes retrieved (MD = 1.30, 95%CI [1.21, 1.40], p < 0.00001), and E2 levels on the day of hCG (SMD = 0.37, 95%CI [0.07, 0.66], p = 0.01), along with a reduction in cycle cancellation rate (OR = 0.60, 95%CI [0.44, 0.83], p = 0.002), miscarriage rate (OR = 0.38, 95%CI [0.15, 0.98], p = 0.05), total days of Gn applied (MD = -0.89, 95%CI [-1.37, -0.41], p = 0.0003), and total dose of Gn used (MD = -330.44, 95%CI [-373.93, -286.96], p < 0.00001). The sensitivity analysis indicated that our pooled results were robust. CONCLUSIONS: These findings suggested that CoQ10 pretreatment is an effective intervention in improving IVF/ICSI outcomes for women with DOR. Still, this meta-analysis included relatively limited sample sizes with poor descriptions of their methodologies. Rigorously conducted trials are needed in the future.
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Fertilización In Vitro , Reserva Ovárica , Índice de Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Inyecciones de Esperma Intracitoplasmáticas , Ubiquinona , Humanos , Ubiquinona/análogos & derivados , Ubiquinona/uso terapéutico , Ubiquinona/administración & dosificación , Ubiquinona/farmacología , Femenino , Reserva Ovárica/efectos de los fármacos , Embarazo , Inyecciones de Esperma Intracitoplasmáticas/métodos , Fertilización In Vitro/métodos , Infertilidad Femenina/terapia , Infertilidad Femenina/tratamiento farmacológico , Adulto , Inducción de la Ovulación/métodosRESUMEN
PURPOSE: This study aimed to compare the fixed and flexible protocols for progestin-primed ovarian stimulation (PPOS) in poor ovarian responders. METHODS: This retrospective study included 95 poor ovarian responders classified using the Patient-Oriented Strategies Encompassing Individualized Oocyte Number group 4 criteria. Treatment involved assisted reproductive medicine using fixed and flexible PPOS protocols at Shiga University of Medical Science between July 2019 and August 2023. PPOS cycles were assigned to the fixed and flexible groups at the discretion of attending physicians. The results of assisted reproductive medicine were compared between groups. RESULTS: The fixed and flexible groups included 68 and 27 patients, respectively. The flexible group obtained more retrieved oocytes and two pro-nuclei than the fixed group, without an early luteinizing hormone surge. Multiple linear regression analysis demonstrated that differences in protocols and anti-müllerian hormone (AMH) levels were related to the number of retrieved oocytes. The differences in protocols were more strongly correlated with the number of oocytes than with the AMH levels. CONCLUSION: Among poor ovarian responders, the flexible PPOS protocol provided more retrieved oocytes than the fixed PPOS protocol, possibly because the total dosage of progestins was lower in the flexible group and progestins were not administered at the time when ovarian stimulation was initiated.
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Recuperación del Oocito , Inducción de la Ovulación , Progestinas , Humanos , Femenino , Inducción de la Ovulación/métodos , Adulto , Estudios Retrospectivos , Progestinas/uso terapéutico , Hormona Antimülleriana/sangre , Oocitos/efectos de los fármacos , Hormona Luteinizante/sangreRESUMEN
PURPOSE: Fertility issues are of great concern for young women undergoing treatment for breast cancer (BC). Fertility preservation (FP) protocols using controlled ovarian stimulation (COS) with letrozole have been widely used with overall good results. However, letrozole cannot be used in every country in this context. This study aimed to assess the efficacy of tamoxifen for COS in women with early BC undergoing FP. METHODS: This multicentric prospective study included patients aged 18-40, diagnosed with stage I, II and III invasive BC, undergoing tamoxifen-COS before adjuvant or neoadjuvant chemotherapy (NAC). The primary endpoint was the efficacy of tamoxifen-COS protocol evaluated by the number of oocytes collected and vitrified. Secondary endpoints included the time interval before chemotherapy, breast cancer (BC) recurrence rates, and reproductive outcomes. RESULTS: Ninety-five patients were included between 2014 and 2017, aged 31.5 ± 4 years on average. 37.9 % received NAC and 62.1 % received adjuvant chemotherapy. FP procedure was successful in 89.5 % of the cycles. The mean number of collected and vitrified oocytes was 12.8 ± 7.9 and 9.8 ± 6.2, respectively. The mean duration of COS was 10.4 ± 1.9 days. Median time before chemotherapy initiation was 3.6 weeks (IQR 3.1; 4.1) for women receiving NAC. Five-year relapse-free and overall survival rates were in-line with those expected in this population. Twenty-one women had spontaneous full-term pregnancies, while 5 underwent IVF cycles with frozen-thawed oocytes, without pregnancy. CONCLUSION: Tamoxifen-COS protocols appear to be feasible before adjuvant or NAC treatment in young BC patients and efficient in terms of oocyte yield.
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Neoplasias de la Mama , Preservación de la Fertilidad , Inducción de la Ovulación , Tamoxifeno , Humanos , Femenino , Preservación de la Fertilidad/métodos , Neoplasias de la Mama/tratamiento farmacológico , Tamoxifeno/administración & dosificación , Adulto , Estudios Prospectivos , Inducción de la Ovulación/métodos , Estudios de Seguimiento , Antineoplásicos Hormonales/administración & dosificación , Quimioterapia Adyuvante , Adulto Joven , Embarazo , Terapia Neoadyuvante/métodos , Letrozol/administración & dosificación , Letrozol/uso terapéutico , Índice de Embarazo , Adolescente , Recuperación del Oocito/métodos , Criopreservación/métodosRESUMEN
Planned oocyte cryopreservation (OC) has the potential to address the burden of the biological clock, giving women and individuals with ovaries more autonomy in choosing when to have children and with whom. In the United States, the annual number of OC cycles has grown significantly, yet many questions remain regarding planned OC. The field is starting to gather data on the clinical practice and social perspectives around planned oocyte cryopreservation, including the optimal age range at which to offer planned OC, what factors are most predictive of a successful outcome, and the optimal number of oocytes and ovarian stimulation cycles to achieve a live birth. There is a clear need for setting realistic expectations about the chance of success with OC; however, most patients have yet to return to thaw their oocytes, and outcomes data are limited. Clinical models have been developed to predict OC success based on surrogate markers such as age, number of oocytes retrieved, and anti-Müllerian hormone level. Patient education should emphasize the age-related decline in fertility, that eggs do not equal embryos, and that more than one cycle may be needed to obtain sufficient oocytes to have a reasonable chance of future success. While planned OC is not quite an insurance policy against future reproductive challenges, it provides the best option to date for expanding the reproductive window and maximizing reproductive options while navigating individual life circumstances in the context of family building.
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Criopreservación , Preservación de la Fertilidad , Oocitos , Humanos , Femenino , Preservación de la Fertilidad/métodos , Inducción de la Ovulación , Recuperación del Oocito , Estados Unidos , Adulto , EmbarazoRESUMEN
RESEARCH QUESTION: Can inadvertent pregnancies go unnoticed when initiating random-start ovarian stimulation (RSOS) despite monitoring? DESIGN: Case series at a university-based tertiary care fertility clinic. RESULTS: Between June 2022 and December 2023, two cases of undetected early pregnancy at the onset of RSOS were identified, both leading to severe ovarian hyperstimulation syndrome (OHSS) with hospitalization. CONCLUSION: RSOS protocols add flexibility in fertility clinics when there is no intention of a fresh embryo transfer, but may be associated with insidious risk of OHSS. The authors advocate for comprehensive consultation and serial monitoring of human chorionic gonadotrophin during ovarian stimulation, while cautioning against over-reliance on baseline hormone concentrations when initiating RSOS. If the benefits of RSOS seem limited, healthcare providers should consider delaying ovarian stimulation to avert health, but also medicolegal and financial, complications.
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Síndrome de Hiperestimulación Ovárica , Inducción de la Ovulación , Humanos , Femenino , Embarazo , Inducción de la Ovulación/efectos adversos , Inducción de la Ovulación/métodos , AdultoRESUMEN
Background and Objectives: Polycystic ovarian syndrome (PCOS) is a widespread endocrine disorder affecting 5-18% of females in their childbearing age. The aim of this study is to assess the efficacy of combining a low dosage of human chorionic gonadotropin (HCG) along with clomiphene citrate (CC) for stimulating ovulation in infertile women diagnosed with CC-resistant PCOS. Materials and Methods: A randomized controlled trial was carried out on 300 infertile CC-resistant PCOS women. All participants were assigned to two groups: the CC-HCG group and the CC-Placebo group. Subjects in the CC-HCG group were given CC (150 mg/day for 5 days starting on the 2nd day of the cycle) and HCG (200 IU/day SC starting on the 7th day of the cycle). Subjects in the CC-Placebo group were given CC and a placebo. The number of ovarian follicles > 18 mm, cycle cancellation rate, endometrial thickness, ovulation rate, clinical pregnancy rate, and occurrence of early ovarian hyper-stimulation syndrome were all outcome variables in the primary research. Results: Data from 138 individuals in the CC-HCG group and 131 participants in the CC-Placebo group were subjected to final analysis. In comparison to the CC-Placebo group, the cycle cancellation rate in the CC-HCG group was considerably lower. The CC-HCG group exhibited a substantial increase in ovarian follicles reaching > 18 mm, endometrial thickness, and ovulation rate. The clinical pregnancy rate was higher in the CC-HCG group (7.2% vs. 2.3%; CC-HCG vs. CC-Placebo). Upon adjusting for BMI and age, the findings of our study revealed that individuals in the CC-HCG group who had serum prolactin levels below 20 (ng/mL), secondary infertility, infertility duration less than 4 years, baseline LH/FSH ratios below 1.5, and serum AMH levels more than 4 (ng/mL) had a higher likelihood of achieving pregnancy. In the CC-Placebo group, there was a greater prediction of clinical pregnancy for those with serum AMH (<4), primary infertility, serum prolactin ≤ 20 (ng/mL), baseline LH/FSH < 1.5, and infertility duration < 4 years. Conclusions: The use of a small dose of HCG along with CC appeared to be an effective treatment in reducing cycle cancelation, improving the clinical pregnancy rate and ovulation rate in CC-resistant PCOS patients. The trial was registered with Clinical Trials.gov, identifier NCT02436226.
Asunto(s)
Gonadotropina Coriónica , Clomifeno , Infertilidad Femenina , Inducción de la Ovulación , Síndrome del Ovario Poliquístico , Humanos , Femenino , Clomifeno/uso terapéutico , Clomifeno/administración & dosificación , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/fisiopatología , Inducción de la Ovulación/métodos , Gonadotropina Coriónica/administración & dosificación , Gonadotropina Coriónica/uso terapéutico , Gonadotropina Coriónica/sangre , Adulto , Embarazo , Infertilidad Femenina/tratamiento farmacológico , Infertilidad Femenina/etiología , Fármacos para la Fertilidad Femenina/uso terapéutico , Fármacos para la Fertilidad Femenina/administración & dosificación , Índice de Embarazo , Resultado del TratamientoRESUMEN
The objective of this study was to evaluate clinical outcomes for patients undergoing IVF treatment where an artificial intelligence (AI) platform was utilized by clinicians to help determine the optimal starting dose of FSH and timing of trigger injection. This was a prospective clinical trial with historical control arm. Four physicians from two assisted reproductive technology treatment centers in the United States participated in the study. The treatment arm included patients undergoing autologous IVF cycles between December 2022-April 2023 where the physician use AI to help select starting dose of follicle stimulating hormone (FSH) and trigger injection timing (N = 291). The control arm included historical patients treated where the same doctor did not use AI between September 2021 and September 2022. The main outcome measures were total FSH used and average number of mature metaphase II (MII) oocytes. There was a non-significant trend towards improved patient outcomes and a reduction in FSH with physician use of AI. Overall, the average number of MIIs in the treatment vs. control arm was 12.20 vs 11.24 (improvement = 0.96, p = 0.16). The average number of oocytes retrieved in the treatment vs. control arm was 16.01 vs 14.54 (improvement = 1.47, p = 0.08). The average total FSH in the treatment arm was 3671.95 IUs and the average in the control arm was 3846.29 IUs (difference = -174.35 IUs, p = 0.13). These results suggests that AI can safely assist in refining the starting dose of FSH while narrowing down the timing of the trigger injection during ovarian stimulation, benefiting the patient in optimizing the count of MII oocytes retrieved.
Asunto(s)
Fertilización In Vitro , Hormona Folículo Estimulante , Aprendizaje Automático , Oocitos , Inducción de la Ovulación , Humanos , Femenino , Estudios Prospectivos , Adulto , Hormona Folículo Estimulante/administración & dosificación , Inducción de la Ovulación/métodos , Fertilización In Vitro/métodos , Oocitos/citología , Recuperación del Oocito/métodos , EmbarazoRESUMEN
RESEARCH QUESTION: Does luteinizing hormone (LH) levels on human chorionic gonadotropin (HCG) trigger day (LHHCG) affect the clinical outcomes of patients with diminished ovarian reserve (DOR) undergoing gonadotropin-releasing hormone antagonist (GnRH-ant) protocol? METHODS: Retrospective analysis fresh embryo transfer cycles of DOR patients who underwent GnRH-ant protocol from August 2019 to June 2023. The participants were divided into different groups according to LHHCG level and age. The clinical data and outcomes were compared between groups. RESULTS: In patients with DOR, the HCG positive rate (59.3% versus 39.8%, P = 0.005), embryo implantation rate (34.5% versus 19.7%, P = 0.002), clinical pregnancy rate (49.2% versus 28.4%, P = 0.003), live birth rate (41.5% versus 22.7%, P = 0.005) in LHHCG < 2.58 IU/L group were significantly higher than LHHCG ≥ 2.58 IU/L group. There was no significant correlation between LHHCG level and clinical pregnancy in POSEIDON group 3. In POSEIDON group 4, the HCG positive rate (52.8% versus 27.0%, P = 0.015), embryo implantation rate (29.2% versus 13.3%, P = 0.023), clinical pregnancy rate (45.3% versus 18.9%, P = 0.010) in LHHCG < 3.14 IU/L group were significantly higher than LHHCG ≥ 3.14 IU/L group. Logistic regression analysis indicated that LHHCG level was an independent influencing factor for clinical pregnancy in POSEIDON group 4 patients (OR = 3.831, 95% CI: 1.379-10.643, P < 0.05). CONCLUSIONS: LHHCG level is an independent factor affecting pregnancy outcome of fresh embryo transfer in DOR patients undergoing GnRH-ant protocol, especially for advanced-aged women. LHHCG had a high predictive value for POSEIDON group 4 patients, and LHHCG ≥ 3.14 IU/L predicts poor pregnancy outcomes.
Asunto(s)
Gonadotropina Coriónica , Transferencia de Embrión , Hormona Liberadora de Gonadotropina , Hormona Luteinizante , Reserva Ovárica , Inducción de la Ovulación , Índice de Embarazo , Humanos , Femenino , Embarazo , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Hormona Luteinizante/sangre , Gonadotropina Coriónica/administración & dosificación , Gonadotropina Coriónica/uso terapéutico , Adulto , Estudios Retrospectivos , Reserva Ovárica/efectos de los fármacos , Reserva Ovárica/fisiología , Inducción de la Ovulación/métodos , Transferencia de Embrión/métodos , Fertilización In Vitro/métodos , Antagonistas de Hormonas/uso terapéutico , Antagonistas de Hormonas/administración & dosificación , Resultado del Tratamiento , Infertilidad Femenina/terapia , Infertilidad Femenina/sangre , Infertilidad Femenina/tratamiento farmacológico , Resultado del Embarazo/epidemiologíaRESUMEN
Introduction: In vitro fertilization (IVF) is a technology that assists couples experiencing infertility to conceive children. However, unsuccessful attempts can lead to significant physical and financial strain. Some individuals opt for electro-acupuncture (EA) during IVF, even though there is limited evidence regarding the efficacy of this practice. Thus, this pilot study aims to explore the effectiveness and safety of EA during IVF on pregnancy outcomes. Methods and analysis: This clinical trial is a parallel, randomized, sham-controlled study. It aims to include a total of 118 infertile women who intend to undergo IVF. The participants will be randomly divided into three groups in a 1:1:1 ratio: the EA + IVF group, the placebo electro-acupuncture (pEA) +IVF group, and the IVF control group. All of the patients will be required to use ovarian stimulation drugs, while those in the EA + IVF and pEA + IVF groups will receive acupuncture treatment at three sessions per week (every other day) until trigger day with a minimum five session. The primary outcome of this trial will focus on the clinical pregnancy rate (CPR). CPR is defined as the rate of achieving clinical pregnancy from the first fresh/frozen embryo transfer cycle with an ultrasound-confirmed gestational sac in the uterine cavity. The secondary outcomes will assess embryology data, biochemical pregnancy rate, early miscarriage rate, Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Fertile Quality of Life (FertiQoL), patient retention rate, treatment adherence, and safety outcomes. Ethics and dissemination: Ethics approval was obtained from the Ethics Committee of Sichuan Jinxin Xi'nan Women and Children Hospital (number 2021-007). The results will be disseminated through peer-reviewed publications. The participants gave informed consent to participate in the study before taking part in it. Clinical trial registration: https://www.chictr.org.cn, identifier ChiCTR2300074455.
Asunto(s)
Electroacupuntura , Fertilización In Vitro , Resultado del Embarazo , Índice de Embarazo , Humanos , Femenino , Embarazo , Fertilización In Vitro/métodos , Electroacupuntura/métodos , Proyectos Piloto , Adulto , Infertilidad Femenina/terapia , Inducción de la Ovulación/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Introduction: the availability of oocytes is fundamental to in vitro fertilization (IVF). The factors associated with optimal or suboptimal oocyte recovery rates (ORR) in low-resource settings are not well known. This study aimed to determine the factors associated with ORR by comparing demographic and IVF cycle data of women undergoing IVF in our Centre. Methods: this was a prospective study of 110 infertile women undergoing IVF at Nisa Premier Hospital, Abuja Nigeria, from October 2020 to September 2021. All women had reached the stage of oocyte retrieval or further, after receiving ovarian stimulation with our routine protocols. Treatment was monitored by serial transvaginal ultrasonography. The oocyte retrieval procedures were performed under conscious sedation, 36 hours after the ovulatory trigger. Optimal ORR was when eggs were obtained from at least 80% of follicles punctured. Sub-optimal ORR was when it was less than 80%. Data analyses utilized SPSS statistical software and a p-value of < 0.05 was considered significant. Results: the mean age of all women was 34.1±4.9 years. Sixty-nine women (62.7%) had sub-optimal ORR while 41 (37.3%) had optimal ORR. Six women (5.5%) had no oocytes retrieved. Significantly more women with sub-optimal ORR were obese (70.6 vs 29.4%) and had higher follicle-stimulating hormone (FSH) levels (8.11 vs 6.34 miu/ml), p-value- 0.039. Women with sub-optimal ORR had higher mean prolactin levels (17.10 ± 13.93 miu/ml) than women with optimal ORR 11.43 ± 6.65 miu/ml), p-value- 0.019). Significantly more oocytes (5.99 vs 10.37, p-value 0.001), and MII oocytes (5.78 vs 7.56, p-value 0.035) were retrieved in women with optimal than sub-optimal ORR. The duration of stimulation, total amounts of gonadotropins administered, and fertilized oocytes were not significantly different among both groups (p-value >0.05). Conclusion: this study has shown the factors associated with ORR in our setting to be basal FSH, prolactin, and obesity.
Asunto(s)
Fertilización In Vitro , Infertilidad Femenina , Recuperación del Oocito , Oocitos , Inducción de la Ovulación , Humanos , Femenino , Adulto , Recuperación del Oocito/métodos , Fertilización In Vitro/métodos , Estudios Prospectivos , Nigeria , Inducción de la Ovulación/métodos , Infertilidad Femenina/terapia , Oocitos/fisiología , Embarazo , ObesidadRESUMEN
STUDY QUESTION: Does luteal estradiol (E2) pretreatment give a similar number of retrieved oocytes compared to no-pretreatment in advanced-aged women stimulated with corifollitropin alfa in an antagonist protocol? SUMMARY ANSWER: Programming antagonist cycles with luteal E2 gave similar number of retrieved oocytes compared to no-pretreatment in women aged 38-42 years. WHAT IS KNOWN ALREADY: Programming antagonist cycles with luteal E2 pretreatment is a valuable tool to organize the IVF procedure better and is safe without any known impact on cycle outcome. However, variable effects were observed on the number of retrieved oocytes depending on the treated population. In advanced-age women, recruitable follicles tend to decrease in number and to be more heterogeneous in size but it remains unclear if estradiol pretreatment could change the oocyte yield through its negative feed-back effect on FSH intercycle rise. STUDY DESIGN, SIZE, DURATION: This non-blinded randomized controlled non-inferiority trial was conducted between 2016 and 2022 with centrally computerized randomization and concealed allocation. Participants were 324 women aged 38-42 years undergoing IVF treatment. The primary endpoint was the total number of retrieved oocytes. Statistical analysis was performed with one-sided alpha risk of 2.5% and 95% confidence interval (CI) with the non-inferiority of E2 pretreatment proved by a P value <0.025 and a lower delta margin of the CI within two oocytes compared to no pretreatment. Secondary endpoints were duration and total dosage of recombinant FSH, cancellation rate, percentage of oocyte pick-up (OPU) on working days, total number of metaphase II oocytes and obtained embryos, fresh transfer live birth rate, and cumulative live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: This multicentric study enrolled women with regular cycles, weight >50 kg and body mass index <32, IVF cycle 1-2. According to randomization, micronized estradiol 2 mg twice a day was started on days 20-24 and continued until Wednesday beyond the onset of menses followed by administration of corifollitropin alfa on Friday, i.e. stimulation (S)1 or from D1-3 of a natural cycle in unpretreated patients. GnRH antagonist was started at S6 and additional FSH at S8. MAIN RESULTS AND THE ROLE OF CHANCE: Basal characteristics were similar in patients randomized in E2 pretreated (n = 164) and non-pretreated (n = 160) groups (intended to treat (ITT) population). A total of 291 patients started treatment (per protocol (PP) population), 147 in E2 pretreated group with a mean number [SD] of pre-treatment days 9.8 [2.6] and 144 in the non-pretreated group. Despite advanced age, oocyte yields ranged from 0 to 29 in both groups with a median number of 6 retrieved oocytes in accordance with a mean anti-Müllerian hormone (AMH) level above 1.2 ng/ml. We demonstrated the non-inferiority of E2 pretreatment with a mean difference of -0.1 oocyte 95% CI [-1.5; 1.3] P = 0.004 in the PP population and a mean difference of -0.44 oocyte [-1.84; 0.97] P = 0.014 in the ITT population. Oocyte retrieval was more often on working days in E2 pretreated patients (91.9 versus 74.2%, P < 0.001). In patients reaching OPU, the duration of stimulation was statistically significantly longer (11.7 [1.7] versus 10.8 [1.8] days, P < 0.001) and the extra FSH dosage in addition to corifollitropin alfa was statistically significantly higher (1040 [548] versus 778 [504] IU, P < 0.001) in E2 pretreated than non-pretreated patients. We did not observe any significant differences in the number of retrieved oocytes (8.4 [6.1] versus 9.1 [6.0]), in the number of Metaphase 2 oocytes (7 [5.5] versus 7.3 [5.2]) nor in the number of obtained embryos (5 [4.6] versus 5.2 [4.2]) in E2 pretreated patients compared to non-pretreated patients. The live birth rate after fresh transfer (16.2% versus 18.5%, respectively), and the cumulative live birth rate per patient (17.7% versus 22.9%, respectively) were similar in both groups. Among the PP population, 31.6% of patients fulfilled the criteria for group 4 of Poseïdon classification (AMH <1.2 ng/ml and/or antral follicle count <5). In this sub-group of patients, we observed in contrast a statistically higher number of retrieved oocytes in E2 pretreated patients compared to non-pretreated (5.1 [3.8] versus 3.4 [2.7], respectively, the mean difference of +1.7 oocyte [0.2; 3.2] P = 0.022) but without significant difference in the cumulative live birth rate per patient (15.7% versus 7.3%, respectively). LIMITATIONS, REASONS FOR CAUTION: Our stimulated women older than 38 years obtained a wide range of collected oocytes suggesting very different stages of ovarian aging in both groups. E2 pretreatment is more likely to increase oocyte yield at the stage of ovarian aging characterized by asynchrony of a reduced follicular cohort. Another limitation is the sample size in sub-group analysis of patients with AMH <1.2 ng/ml. Finally, the absence of placebo for pretreatment could also introduce possible bias. WIDER IMPLICATIONS OF THE FINDINGS: Programming antagonist cycles with luteal E2 pretreatment seems a useful tool in advanced age women to better schedule oocyte retrievals on working days. However, the potential benefit of the number of collected oocytes remains to be demonstrated in a larger population displaying the characteristics of decreased ovarian reserve encountered in Poseïdon classification. STUDY FUNDING/COMPETING INTEREST(S): Research grant from (MSD) Organon, France. I.C., S.D., B.B., X.M., S.G., and C.J. have no conflict of interest with this study. I.C.D. declares fees as speaker from Merck KGaA, Gedeon Richter, MSD (Organon, France), Ferring, Theramex, and IBSA and participation on advisory board from Merck KGaA. I.C.D. also declares consulting fees, and travel and meeting support from Merck KGaA. N.M. declares grants paid to their institution from MSD (Organon, France); consulting fees from MSD (Organon, France), Ferring, and Merck KGaA; honoraria from Merck KGaA, General Electrics, Genevrier (IBSA Pharma), and Theramex; support for travel and meetings from Theramex, Merck KGaG, and Gedeon Richter; and equipment paid to their institution from Goodlife Pharma. N.C. declares grants from IBSA Pharma, Merck KGaA, Ferring, and Gedeon Richter; support for travel and meetings from IBSA Pharma, Merck KGaG, MSD (Organon, France), Gedeon Richter, and Theramex; and participation on advisory board from Merck KGaA. A.G.L. declares fees as speaker from Merck KGaA, Gedeon Richter, MSD (Organon, France), Ferring, Theramex, and IBSA. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02884245. TRIAL REGISTRATION DATE: 29 August 2016. DATE OF FIRST PATIENT'S ENROLMENT: 4 November 2016.
Asunto(s)
Estradiol , Fertilización In Vitro , Hormona Folículo Estimulante Humana , Recuperación del Oocito , Inducción de la Ovulación , Índice de Embarazo , Humanos , Femenino , Adulto , Hormona Folículo Estimulante Humana/administración & dosificación , Inducción de la Ovulación/métodos , Estradiol/administración & dosificación , Embarazo , Recuperación del Oocito/métodos , Fertilización In Vitro/métodos , Fase Luteínica/efectos de los fármacos , Tasa de NatalidadRESUMEN
OBJECTIVE: To study hemodynamic changes along controlled ovarian stimulation in women undergoing in vitro fertilization. STUDY DESIGN: Prospective observational cohort study conducted at Mother and Child Department of University Hospital Federico II, in Naples, Italy, between April 2021 and July 2022. Sixty-eight infertile patients undergoing controlled ovarian stimulation with gonadotropin, antagonist protocol and a fresh embryo transfer were included. Haemodynamic assessment was carried out using UltraSonic Cardiac Output Monitor at baseline (T1), estradiol peak (T2), fresh embryo-transfer day (T3). To evaluate relationships between quantitative variables and groups a Student T test for independent data was assessed. One-way analysis of variance (ANOVA) was used to determine the differences between the means of three time points (T1, T2 and T3) for quantitative variables. A mixed-model analysis of variance (ANOVA) was used to determine the differences between groups, among time points (T1, T2 and T3). RESULTS: Sixty-eight patients were included. Significant differences over the three time points have been observed for CO (f = 3.78 l/min; p = 0.025), SVI (f = 3.56 ml/m2;p = 0.013), and RSVI (f = 4.84 dscm-5 m2; p = 0.009). No significant differences in trends have been found between beta hCG positive and beta hCG negative groups. There were no significant differences in maternal hemodynamic parameters at time-point T3 between patients treated with hCG 10,000 UI and with Triptorelin. Patients considered at increased risk of hyperstimulation reported a significant increase in SVI at baseline (26.9 ± 9.0 mL/m2 vs 21.9 ± 7.0 mL/m2; p = 0.010). CONCLUSION: According to the results of our study, during controlled ovarian stimulation with antagonist protocol, patients undergo significant changes in maternal cardiovascular parameters over a very short period.