RESUMO
OBJECTIVE: To disclose the relationships between serum LH and reproductive outcomes in Gonadotropin-releasing hormone (GnRH) antagonist protocol pretreated with luteal estradiol. METHODS: 371 patients, pretreated with estradiol, followed the GnRH antagonist protocol. They were divided into four groups based on the quartiles of serum LH levels on the day of gonadotropin (Gn) initiation(LHGI) and trigger (LHtrigger). Data on various pregnancy outcomes were collected. RESULTS: As serum LHGI increased, anti-Müllerian hormone (AMH) level, antral follicle count (AFC), LHtrigger, estradiol (E2) and P on the trigger day, E2/oocytes, and oocyte numbers increased and peaked in Q4, while Gn dose decreased. Good-quality embryo and blast formation rates increased and peaked in Q3. LHGI <3.93 mIU/ml impaired ongoing pregnancy rate and LBR. After adjusting for AMH and AFC, the impacts were not significant. As LHtrigger increased, E2/oocytes and good-quality embryo rate increased and peaked in T4 and implantation rate increased and peaked in T3. LHtrigger <1.49 mIU/ml independently influenced clinical pregnancy rate (CPR) after adjusting for AMH and AFC. LHGI was positively related to AMH, AFC, LHtrigger, blast formation rate and negatively related to BMI, age and Gn dose. LHtrigger was positively related to E2/oocytes and good quality embryo rate. CONCLUSIONS: Lower serum LH represents as a potential indicator for embryo quality and reproductive outcomes in GnRH antagonist fixed protocol pretreated with estradiol. Early identification of excessive suppression of LH levels will benefit individuals with normal ovarian reserve more.
Assuntos
Estradiol , Hormônio Liberador de Gonadotropina , Hormônio Luteinizante , Indução da Ovulação , Resultado da Gravidez , Humanos , Feminino , Gravidez , Estradiol/sangue , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Adulto , Hormônio Luteinizante/sangue , Indução da Ovulação/métodos , Resultado da Gravidez/epidemiologia , Taxa de Gravidez , Antagonistas de Hormônios/administração & dosagem , Estudos Retrospectivos , Fertilização in vitro/métodos , Hormônio Antimülleriano/sangueRESUMO
Purpose: The purpose of this study was to compare the efficacy of Follitropin alpha (Gonal-F) and Follitropin beta (Puregon) on cumulative live birth rate (CLBR), defined as the percentage of the number of patients who delivered for the first time in a single ovarian stimulation cycle and the number of patients in all oocyte retrieval cycles. Methods: A retrospective cohort study including 2864 infertile patients who underwent ovarian stimulation with Puregon (group A, n=1313) and Gonal-F (group B, n=1551) was conducted between July 2015 and June 2021 at a university-affiliated reproductive medicine center. Reduce potential confounding factors between groups, propensity scores and multivariable logistic regression analyses were estimated to obtain unbiased estimates of outcomes. The primary outcome was the difference in CLBR between the two groups. Results: Each group identified 1160 individuals after propensity score matching (PSM). Baseline characteristics were similar between groups after PSM. The total gonadotrophin (Gn) dose (2400 vs 2325), p=0.038) and cost of Gn usage (5327.9¥ vs 7547.2¥, p<0.001) between the Puregon and Gonal-F groups were statistically significant. Nevertheless, the pregnancy outcomes between the two groups were comparable after fresh embryo transfer and subsequent frozen-thawed embryo transfer. Additionally, there was also no difference observed in the primary outcome of CLBR (52.8% vs 55.7%, p=0.169). Multivariable regression analysis revealed that the type of Gn was not associated with CLBR (p = 0.912). Conclusion: Gonal-F may be a reasonable option for infertile patients who are hesitant to receive more Gn dosage injections. Furthermore, Puregon can eliminate unneeded anxiety and expenses while also administering more flexibility. Taken together, these findings could well be utilized in everyday clinical practice to better inform patients when deciding on an ovarian stimulation strategy.
Assuntos
Fertilização in vitro , Hormônio Foliculoestimulante Humano , Humanos , Estudos Retrospectivos , Feminino , Hormônio Foliculoestimulante Humano/administração & dosagem , Adulto , Gravidez , Proteínas Recombinantes/administração & dosagem , Injeções de Esperma Intracitoplásmicas , Indução da Ovulação/métodos , Estudos de CoortesRESUMO
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.
Assuntos
Gonadotropina Coriônica , Estradiol , Fertilização in vitro , Fase Luteal , Indução da Ovulação , Taxa de Gravidez , Progesterona , Humanos , Feminino , Estradiol/sangue , Estradiol/administração & dosagem , Gravidez , Adulto , Gonadotropina Coriônica/administração & dosagem , Fase Luteal/efeitos dos fármacos , Fase Luteal/sangue , Fertilização in vitro/métodos , Progesterona/sangue , Progesterona/administração & dosagem , Estudos Prospectivos , Indução da Ovulação/métodos , Transferência Embrionária/métodos , Recuperação de Oócitos/métodosRESUMO
OBJECTIVE: This research was conducted to assess the therapeutic advantage of combined letrozole and clomiphene citrate versus monotherapy for polycystic ovarian syndrome (PCOS) patients. STUDY DESIGN: Five databases were searched using the search string: (letrozole and clomiphene) AND (clomiphene OR clomiphene citrate OR CC) AND (letrozole OR LE) AND (ovulation induc* OR fertility induc* OR fertility preserv*) AND (polycystic ovarian syndrome OR PCOS). All statistical analyses were conducted in Review Manager 5.4.1. Random effect-effect model was used to pool risk ratio (RR), mean difference (MD), and odds ratio (OR) and their corresponding 95% confidence interval (CI). Moreover, qualitative analysis was conducted to qualitatively analyze ovulation, secondary outcomes, and cycle characteristics. RESULTS: One clinical trial and three randomized clinical trials (RCTs) were used in the study. Two studies were used in a quantitative analysis showing that combination was superior for ovulation induction (RR = 1.86 [1.37, 2.53]; p < 0.0001; I2 = 0%), but the number of follicles ≥15 mm was significantly associated with the combination (MD = 0.40[0.14, 0.66]; p = 0.002; I2 = 0%). On subgroup analysis, only hot flushes were significantly associated with the combination (RR = 2.67[1.12, 6.36]; p = 0.03; I2 = 0%). The meta-analysis of two studies reported a significantly higher ovulation rate and number of dominant follicles in the combination therapy group compared with the LE alone arm but no significant difference in pregnancy rate, endometrial thickness, and adverse events. CONCLUSION: Our study demonstrates a significant effect of the combination on ovulation induction. The combination yielded a better chance of conception and viable pregnancy. Further studies are needed to determine the live birth rate. HighlightsCombined Letrozole and Clomiphene is superior to either of these drugs alone for ovulation induction in PCOS.Our results conclude that the combination results in better ovulation, cycle characteristics, and secondary changes.Only the incidence of hot flushes as an adverse effect is increasingly reported in combination.
Assuntos
Clomifeno , Quimioterapia Combinada , Fármacos para a Fertilidade Feminina , Letrozol , Indução da Ovulação , Síndrome do Ovário Policístico , Humanos , Letrozol/administração & dosagem , Letrozol/uso terapêutico , Clomifeno/administração & dosagem , Clomifeno/uso terapêutico , Feminino , Síndrome do Ovário Policístico/tratamento farmacológico , Indução da Ovulação/métodos , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/uso terapêutico , Fármacos para a Fertilidade Feminina/efeitos adversos , Gravidez , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: The aim of this study was to determine the effects of seasons (winter vs. summer) on oocyte quality in infertile women undergoing ovulation induction for in vitro fertilization. METHODS: This retrospective cross-sectional study assessed 155 cycles of in vitro fertilization-induced ovulation in women, with 71 and 84 cycles occurring in the summer and winter, respectively. Oocytes were evaluated for quality, with 788 and 713 assessed during summer and winter, and classified according to Nikiforov's categories: (a) category I, good quality; (b) category 2, medium quality; and (c) category 3, low quality. RESULTS: Thickened zona pellucida (p<0.001), increased perivitelline space (p<0.001), oocyte shape abnormalities (p=0.01), and the presence of refractile bodies (p<0.0001) were more frequent in the summer cycles, whereas cytoplasmic granularity (p<0.001) was more frequent in the winter cycles. In winter, we observed a higher frequency of category 3 (p<0.001) and category 2 (p<0.001) oocytes and a lower frequency of category 1 (p<0.001) oocytes. CONCLUSION: Oocyte dysmorphisms were found in 70-80% of cases and were more common in winter. The main features include a thickened zona pellucida, enlarged perivitelline space, irregular shape, and cytoplasmic granularity. This implies better-quality oocytes in the summer than in the winter. However, retrospective studies have limitations due to data collection biases and potential confounding variables such as diet and exercise. Future research is needed to confirm these findings and explore the underlying mechanisms.
Assuntos
Fertilização in vitro , Oócitos , Estações do Ano , Humanos , Feminino , Estudos Retrospectivos , Estudos Transversais , Oócitos/fisiologia , Adulto , Infertilidade Feminina/terapia , Indução da OvulaçãoRESUMO
The objective of study was to characterize HPV in vaginal samples from women being seen at the Center for Reproductive Medicine and Infertility at Weill Cornell Medicine before and following ovarian stimulation. A total of 29 women made samples available for analysis by viral metagenomics. Eighteen women were HPV-positive, six (33.3%) at their initial visit and 15 (83.3%) following hormone stimulation (p = 0.0059). Pairwise comparison of nucleotide sequences and phylogenetic analysis showed the classification sequences into two genera: Alphapapillomavirus and Gammapapillomavirus. Sequences were from 8 HPV types: HPV 51 (n = 2), HPV 68 (n = 1), HPV 83 (n = 9), HPV 84 (n = 2), HPV 121 (n = 6), HPV 175 (n = 1) and HPV 190 (n = 1). Additionally, C16b and C30 likely represent new types. In summary, multiple HPV types are present in the vagina of reproductive age women and are induced by hormone used to stimulate ovulation.
Assuntos
Indução da Ovulação , Papillomaviridae , Infecções por Papillomavirus , Filogenia , Vagina , Humanos , Feminino , Vagina/virologia , Infecções por Papillomavirus/virologia , Adulto , Papillomaviridae/genética , Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , DNA Viral/genética , Análise de Sequência de DNA , Adulto Jovem , Metagenômica , Genótipo , Papillomavirus HumanoRESUMO
BACKGROUND: Controlled ovarian stimulation is a common skill of assisted reproductive technologies (ARTs). In the clinic, some females would undergo more than one controlled ovarian stimulation cycle. However, few studies have focused on the influence of multi-superovulation on oocytes and offspring. RESULTS: Here, we found that multi-superovulation disrupted the transcriptome of oocytes and that the differentially expressed genes (DEGs) were associated mainly with metabolism and fertilization. The disruption of mRNA degradation via poly (A) size and metabolism might be a reason for the reduced oocyte maturation rate induced by repeated superovulation. Multi-superovulation results in hypo-genomic methylation in oocytes. However, there was an increase in the methylation level of CGIs. The DMRs are not randomly distributed in genome elements. Genes with differentially methylated regions (DMRs) in promoters are enriched in metabolic pathways. With increasing of superovulation cycles, the glucose and insulin tolerance of offspring is also disturbed. CONCLUSIONS: These results suggest that multi-superovulation has adverse effects on oocyte quality and offspring health.
Assuntos
Metilação de DNA , Oócitos , Superovulação , Oócitos/metabolismo , Metilação de DNA/genética , Feminino , Superovulação/genética , Superovulação/efeitos dos fármacos , Animais , Humanos , Transcriptoma/genética , Camundongos , Indução da Ovulação/métodos , Ilhas de CpG/genéticaRESUMO
The objective of the study was to characterise the expression patterns of the two key components of cortisol action namely HSD11B1 (11-beta-hydroxysteroid dehydrogenase type 1) and NR3C1 (nuclear receptor subfamily 3, group C, member 1, also known as the glucocorticoid receptor) in superovulation induced bovine follicles during the periovulation and subsequent corpus luteum (CL) formation. Bovine ovaries containing preovulatory follicles or CL were timely defined during induced ovulation as follows: 0 h before GnRH (Gonadotropin-releasing hormone) application, and 4, 10, 20, 25 (follicles) and 60 h (early CL) after GnRH. The low mRNA expression of HSD11B1 and NR3C1 in the follicle group before the GnRH application increased significantly in the follicle group 20 h after GnRH and remained high afterward also in the early CL group. In contrast, the high NR3C1 mRNA decreased in follicles 25 h after GnRH (close to ovulation) and significantly increased again after ovulation (early CL). Our results indicated the involvement of HSD11B1 and NR3C1 as the two key components of cortisol action in the local mechanisms coordinating final follicle maturation, ovulation, follicular-luteal transition and CL development in the cow.
Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1 , Corpo Lúteo , Hormônio Liberador de Gonadotropina , Folículo Ovariano , Receptores de Glucocorticoides , Animais , Feminino , Bovinos/fisiologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genética , Hormônio Liberador de Gonadotropina/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Indução da Ovulação/veterinária , Ovulação/fisiologia , Regulação da Expressão GênicaRESUMO
This study aimed to evaluate the effect of different growth hormone (GH) pretreatment times in assisted reproductive therapy in patients with diminished ovarian reserve (DOR). A retrospective pilot cohort analysis was performed on patients with DOR receiving GH pretreatment in the Assisted Reproduction Unit of Sir Run Run Shaw Hospital. A total of 1459 patients met the criteria and were divided into four groups according to GH pretreatment time as follows: 53 were in the 2-month pretreatment group (GH1), 400 were in the 1-month pretreatment group (GH2), 414 were in the ovulation induction period pretreatment group (GH3), and 592 were in the non-GH pretreatment group (control group). In addition, GH1, GH2, and GH3 were combined in the GH pretreatment group. Baseline characteristics and treatment outcomes were compared between the groups. The number of oocytes retrieved in the GH pretreatment, GH1, GH2, and GH3 groups was significantly higher than that in the control group (all Pâ <â .01). The numbers of oocytes retrieved in the GH1 and GH2 groups were similar but were nominally higher than those in the GH3 group. Estradiol concentrations in the GH pretreatment, GH2, and GH3 groups were significantly higher than those in the control group on the day of human chorionic gonadotropin injection (all Pâ <â .01). In the GH1 group, 22 patients had >1 assisted reproductive therapy cycle (non-GH pretreatment) before GH pretreatment, and the number of oocytes retrieved in the GH pretreatment cycle was higher than that in the non-GH pretreatment cycle, but this was not significant. These findings suggest that the GH pretreatment time was appropriately prolonged, and the number of oocytes retrieved nominally increased. In patients with DOR, GH pretreatment improved treatment outcomes. More than 1 month of GH pretreatment did not increase the number of oocytes retrieved.
Assuntos
Hormônio do Crescimento Humano , Reserva Ovariana , Indução da Ovulação , Humanos , Feminino , Estudos Retrospectivos , Projetos Piloto , Adulto , Reserva Ovariana/efeitos dos fármacos , Indução da Ovulação/métodos , Hormônio do Crescimento Humano/uso terapêutico , Hormônio do Crescimento Humano/administração & dosagem , Técnicas de Reprodução Assistida , Fatores de Tempo , Gravidez , Resultado do Tratamento , Taxa de Gravidez , Recuperação de Oócitos/métodosRESUMO
STUDY QUESTION: Can a simplified ovarian hyperstimulation syndrome (OHSS) risk assessment index be developed and validated with sufficient discrimination of moderate/severe OHSS from those without OHSS? SUMMARY ANSWER: This easy-to-use OHSS risk assessment index shows good discriminative power and high calibration accuracy in internal and external validation cohorts. WHAT IS KNOWN ALREADY: An early alert and risk stratification is critical to prevent the occurrence of OHSS. We have previously developed a multi-stage smartphone app-based prediction model to evaluate the risk of OHSS, but app use might not be so convenient in many primary institutions. A simplified OHSS risk assessment index has been required. STUDY DESIGN, SIZE, DURATION: This training and internal validation of an OHSS risk assessment index used retrospective cohort data from January 2016 to December 2020. External validation was performed with a prospective cohort database from January 2021 to May 2022. There were 15 066 cycles in the training cohort, 6502 cycles in the internal validation cohort, and 8097 cycles in the external validation cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was performed in the reproductive medicine center of a tertiary hospital. Infertile women who underwent ovarian stimulation were included. Data were extracted from the local database with detailed medical records. A multi-stage risk assessment index was constructed at multiple stages. The first stage was before the initiation of ovarian stimulation, the second was before the ovulation trigger, the third was after oocyte retrieval, and the last stage was on the embryo transfer day if fresh embryo transfer was scheduled. MAIN RESULTS AND THE ROLE OF CHANCE: We established a simplified multi-stage risk assessment index for moderate/severe OHSS, the performance of which was further evaluated with discrimination and calibration abilities in training and internal and external validation cohorts. The discrimination abilities of the OHSS risk assessment index were determined with C-statistics. C-statistics in training (Stages 1-4: 0.631, 0.692, 0.751, 0.788, respectively) and internal (Stages 1-4: 0.626, 0.642, 0.755, 0.771, respectively) and external validation (Stages 1-4: 0.668, 0.670, 0.754, 0.773, respectively) cohorts were all increased from Stage 1 to 3 with similar trends, and were comparable between Stages 3 and 4. Calibration plots showed high agreement between observed and predicted cases in all three cohorts. Incidences of OHSS based on diverse risk stratification (negligible risk, low risk, medium risk, and high risk) were 0%, 0.6%, 2.7%, and 8.3% in the training cohort, 0%, 0.6%, 3.3%, and 8.5% in the internal validation cohort, and 0.1%, 1.1%, 4.1%, and 7.2% in the external validation cohort. LIMITATIONS, REASONS FOR CAUTION: The influence from clinical interventions including cryopreservation of all embryos cannot be eliminated and thus certain risk factors like estrogen level on trigger day might be assigned with a lower risk score. Another weakness of the study is that several preventive treatments, for instance oral aspirin and letrozole, were not recorded and evaluated in the model. Despite the robust reliability of OHSS assessment index, this tool cannot be used directly for clinical decision-making or as a diagnostic tool. Its value lies in its capacity to evaluate the prognosis of various interventions and to facilitate clinician-patient communication. The combination of this tool and further symptoms and examinations should be all taken into consideration for accurate and personalized management of OHSS. WIDER IMPLICATIONS OF THE FINDINGS: The OHSS risk assessment index can be implemented to facilitate personalized counseling and management of OHSS. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by National Key R&D Program of China (2022YFC2702504), Medical Research Fund Guangdong Provincial (A2024003), and Xinjiang Support Rural Science and Technology (Special Correspondent) Program in Guangdong Province (KTPYJ 2023014). All authors had nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.
Assuntos
Síndrome de Hiperestimulação Ovariana , Indução da Ovulação , Humanos , Síndrome de Hiperestimulação Ovariana/diagnóstico , Feminino , Medição de Risco/métodos , Adulto , Indução da Ovulação/efeitos adversos , Indução da Ovulação/métodos , Estudos Prospectivos , Estudos Retrospectivos , Gravidez , Medicina de Precisão/métodos , Índice de Gravidade de Doença , Taxa de Gravidez , Infertilidade Feminina/terapia , Fertilização in vitro/métodos , Aplicativos MóveisRESUMO
AIM: Luteinizing hormone (LH) plays an important role in ovarian follicle maturation. Human menopausal gonadotropin (hMG) or low dose human chorionic gonadotropin (hCG) can provide LH supplementation during in vitro fertilization (IVF) ovarian stimulation, though studies directly comparing their impact on IVF outcomes are limited. The aim of the study was to determine whether LH supplementation with hMG versus low dose hCG during IVF stimulation affects live birth rate. METHODS: Fresh and frozen embryo transfers (ET) from 2017 to 2021 after standard long or antagonist protocols supplemented with hMG (75-250 IU) or low dose hCG (50-100 IU) during stimulation cycles in our academic center were included. Statistical analysis was performed with T-tests, Mann-Whitney U tests, Chi-square, and multiple linear and logistic regression. RESULTS: Four hundred and sixty eight unique stimulation cycles resulting in 213 fresh and 412 frozen embryo transfers were analyzed. There was a lower mature oocyte yield (10.9 vs. 11.8, p = 0.044) but similar high-quality blastocyst yield (3.6 vs. 3.9, p = 0.11) for hMG vs low dose hCG. Live birth rates per transfer were comparable for fresh (42% vs. 49%, p = 0.24) and frozen (46% vs. 53%, p = 0.45) embryo transfers. Multiple logistic regressions showed no association between supplemental gonadotropin and live birth for both fresh and frozen embryo transfers. CONCLUSION: Fresh and frozen IVF-ET pregnancy outcomes were comparable after hMG versus low dose hCG supplementation, suggesting flexibility in supplemental LH dosing regimens that may address patient or physician preference or cost concerns.
Assuntos
Coeficiente de Natalidade , Gonadotropina Coriônica , Transferência Embrionária , Menotropinas , Indução da Ovulação , Humanos , Feminino , Indução da Ovulação/métodos , Transferência Embrionária/métodos , Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/farmacologia , Adulto , Menotropinas/administração & dosagem , Menotropinas/farmacologia , Gravidez , Nascido Vivo , Hormônio Luteinizante/administração & dosagem , Hormônio Luteinizante/sangue , Criopreservação , Fertilização in vitro/métodos , Estudos RetrospectivosRESUMO
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.
Assuntos
Inibidores da Aromatase , Transferência Embrionária , Fertilização in vitro , Infertilidade Feminina , Letrozol , Sobrepeso , Taxa de Gravidez , Humanos , Letrozol/uso terapêutico , Feminino , Estudos Retrospectivos , Adulto , Gravidez , Inibidores da Aromatase/uso terapêutico , Fertilização in vitro/métodos , Infertilidade Feminina/terapia , Transferência Embrionária/métodos , Indução da Ovulação/métodos , Nascido Vivo , China , Injeções de Esperma IntracitoplásmicasRESUMO
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.
Assuntos
Coeficiente de Natalidade , Fertilização in vitro , Hormônio Liberador de Gonadotropina , Recuperação de Oócitos , Síndrome de Hiperestimulação Ovariana , Indução da Ovulação , Humanos , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Adulto , Recuperação de Oócitos/métodos , Indução da Ovulação/métodos , Estudos Retrospectivos , Gravidez , Estudos de Casos e Controles , Fertilização in vitro/métodos , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Síndrome de Hiperestimulação Ovariana/epidemiologia , Nascido Vivo/epidemiologia , Taxa de Gravidez , Fármacos para a Fertilidade Feminina/uso terapêutico , Fármacos para a Fertilidade Feminina/administração & dosagem , Taiwan/epidemiologia , Injeções de Esperma Intracitoplásmicas/métodosRESUMO
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.
Assuntos
Neoplasias da Mama , Preservação da Fertilidade , Indução da Ovulação , Tamoxifeno , Humanos , Feminino , Preservação da Fertilidade/métodos , Neoplasias da Mama/tratamento farmacológico , Tamoxifeno/administração & dosagem , Adulto , Estudos Prospectivos , Indução da Ovulação/métodos , Seguimentos , Antineoplásicos Hormonais/administração & dosagem , Quimioterapia Adjuvante , Adulto Jovem , Gravidez , Terapia Neoadjuvante/métodos , Letrozol/administração & dosagem , Letrozol/uso terapêutico , Taxa de Gravidez , Adolescente , Recuperação de Oócitos/métodos , Criopreservação/métodosRESUMO
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.
Assuntos
Síndrome de Hiperestimulação Ovariana , Indução da Ovulação , Humanos , Feminino , Gravidez , Indução da Ovulação/efeitos adversos , Indução da Ovulação/métodos , AdultoRESUMO
STUDY QUESTION: Does medroxyprogesterone acetate (MPA) exposure in progestin-primed ovarian stimulation (PPOS) cycles cause molecular perturbations in the steroidogenic function and gonadotropin responsiveness of the granulosa cells? SUMMARY ANSWER: PPOS cycles are identical to traditional GnRH antagonist cycles not only for clinical IVF characteristics but also for gonadotropin receptor expression, response to gonadotropins, and steroidogenic function at the molecular level. WHAT IS KNOWN ALREADY: PPOS is increasingly used as an alternative to GnRH antagonists due to the inhibitory effect of progesterone on LH release by reducing GnRH pulsatility at the hypothalamic level. Although a growing body of evidence from clinical studies did not indicate significant differences between PPOS and antagonist protocols for IVF cycle characteristics and obstetrical outcomes, it is still unknown whether exposure of the antral follicle cohort to progesterone or its synthetic derivatives during ovarian stimulation causes any subtle molecular aberrations in terms of steroidogenesis and gonadotropin responsiveness. To address this issue, detailed comparative molecular analyses were conducted in the luteinized mural granulosa cells (GCs) obtained from normal responding IVF patients undergoing PPOS and antagonist cycles. STUDY DESIGN, SIZE, DURATION: A clinical translational research study was conducted with IVF patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included 55 normal responding IVF patients who underwent ovarian stimulation with either PPOS using MPA (5 mg twice daily) or GnRH antagonist cetrorelix acetate. Recombinant forms of FSH and hCG were used for ovarian stimulation and ovulation triggering, respectively. Luteinized mural GCs obtained during the oocyte retrieval procedure were used for the experiments. Cell culture, quantitative real-time PCR, immunoblotting, confocal time-lapse live cell imaging, and hormone assays were used. MAIN RESULTS AND THE ROLE OF CHANCE: Demographic and IVF cycle characteristics of the patients undergoing ovarian stimulation with PPOS and GnRH antagonist were similar, including ovarian response, mature oocyte yield, and fertilization rates. Molecular analyses revealed that the expression of the enzymes involved in sex-steroid synthesis (StAR, SCC, 3ß-HSD, 17ß-HSD, aromatase) and the uptake/storage/utilization of cholesterol (LDL receptor, Hormone-sensitive lipase, hydroxy-methyl glutaryl Co-enzyme-A reductase, and Sterol O-acyltransferase1) in the GCs of the PPOS cycles were comparable to those of the antagonist cycles. The expression of the receptors for gonadotropins, estrogen, and progesterone hormones was also similar. Basal and hCG-induced increases in 3ß-HSD expression and progesterone production and basal and FSH-induced increases in aromatase expression and E2 output of the GCs from PPOS patients did not exhibit any meaningful differences when compared with GCs from antagonist cycles. Furthermore, basal and hCG-induced up-regulation in the LDL receptor expression and cholesterol uptake did not differ between the groups. Confocal imaging also revealed similar patterns of expression for the steroidogenic enzymes and their co-localization with mitochondria. Lastly, the expression of the other important genes regulating cumulus expansion, ovulation, and luteal function [Relaxin, ADAMTS-1, and epidermal growth factor (EGF)-like growth factor amphiregulin] in the GCs of the PPOS and antagonist cycles were similar. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Caution should be exercised when interpreting our data which was derived from normally responding patients whose ovulation was triggered with hCG. It is unclear whether the molecular parameters assessed vary according to infertility etiologies, magnitude of ovarian response, mode of trigger, and any other underlying ovarian pathologies or systemic diseases. MPA was the progestin used for PPOS and whether these findings can be generalized to other progestins is unknown. WIDER IMPLICATIONS OF THE FINDINGS: This study provides reassuring molecular evidence that exposure of antral follicle cohorts to MPA during the follicular growth phase does not have any detrimental effects on steroidogenic, ovulatory, and luteal functions when compared with GnRH antagonist cycles. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the School of Medicine, the Graduate School of Health Sciences of Koc University and Koç University Research Center for Translational Medicine (KUTTAM), and equally funded by the Republic of Turkey Ministry of Development Research Infrastructure Support Program. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.
Assuntos
Células da Granulosa , Acetato de Medroxiprogesterona , Folículo Ovariano , Indução da Ovulação , Feminino , Humanos , Acetato de Medroxiprogesterona/farmacologia , Indução da Ovulação/métodos , Células da Granulosa/metabolismo , Células da Granulosa/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Adulto , Fertilização in vitro/métodos , Progestinas/farmacologia , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/metabolismo , Gonadotropinas/metabolismoRESUMO
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.
Assuntos
Gonadotropina Coriônica , Clomifeno , Infertilidade Feminina , Indução da Ovulação , Síndrome do Ovário Policístico , Humanos , Feminino , Clomifeno/uso terapêutico , Clomifeno/administração & dosagem , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/fisiopatologia , Indução da Ovulação/métodos , Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/uso terapêutico , Gonadotropina Coriônica/sangue , Adulto , Gravidez , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/etiologia , Fármacos para a Fertilidade Feminina/uso terapêutico , Fármacos para a Fertilidade Feminina/administração & dosagem , Taxa de Gravidez , Resultado do TratamentoRESUMO
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.
Assuntos
Fertilização in vitro , Moxibustão , Indução da Ovulação , Humanos , Feminino , Moxibustão/métodos , Adulto , Indução da Ovulação/métodos , Gravidez , Fertilização in vitro/métodos , Recuperação de Oócitos/métodos , Transferência Embrionária/métodos , Resultado do Tratamento , Infertilidade Feminina/terapia , Taxa de GravidezRESUMO
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.