RESUMO
BACKGROUND: Until now, the sex ratio in a population is believed to be relatively stable with no male/female preponderance. There has been an increasing amount of evidence to suggest that assisted conception may significantly impact on sex ratio (SR). Several factors have been suggested to affect SR such as parental variables (paternal race, maternal age, and body mass index-(BMI), methods of fertilisation (in-vitro fertilisation/intracytoplasmic sperm injection), stage of embryo transfer (cleavage/blastocyst), type of IVF cycle (fresh/cryopreserved), medications used for controlled ovarian stimulation, poor sperm motility, and even culture media. OBJECTIVES: This study aims to investigate the potential impact of the different ART procedures on sex ratio. It will also explore the relationship between paternal race, maternal age and body mass index BMI on sex ratio. METHODS: A retrospective cohort study from January 2017 to December 2023. Participants were women who had successful ART and delivery at Ninewells Assisted Conception Unit (NACU) Dundee and ART centre of Lagos University Teaching Hospital, Nigeria. RESULTS: Overall, 294 (66.2%) of the case records and 150 (33.8%) were evaluated from NACU and LUTH respectively. More male infants 244 (66.8%) were delivered following pregnancies conceived with blastocyst embryo stage transfer when compared with female infants which stood at 121 (33.2%). Concerning cleavage embryo stage transfer, 56 (70.9%) were in favour of female newborns while males accounted for 23 (29.1%). CONCLUSION: The study revealed that there is an increase in the proportion of male babies born following certain assisted conception techniques such as blastocyst stage embryo transfer and IVF while more female babies were born when cleavage stage embryos were transferred or when ICSI was used as a method of fertilisation.
CONTEXTE: Jusqu'à présent, le rapport de masculinité au sein d'une population est considéré comme relativement stable, sans prépondérance masculine/féminine. De plus en plus de preuves suggèrent que la procréation assistée peut avoir un impact significatif sur la sex-ratio (SR). Plusieurs facteurs ont été suggérés pour affecter la SR, tels que les variables parentales (race paternelle, âge maternel et indice de masse corporelle-IMC), les méthodes de fécondation (fécondation in vitro/injection intracytoplasmique de spermatozoïdes), le stade du transfert d'embryon (clivage/blastocyste), le type de Cycle de FIV (frais/cryoconservé), médicaments utilisés pour une stimulation ovarienne contrôlée, mauvaise motilité des spermatozoïdes et même milieux de culture. OBJECTIFS: Cette étude vise à étudier l'impact potentiel des différentes procédures de TAR sur le sex-ratio. Il explorera également la relation entre les variables parentales telles que la race paternelle, l'âge de la mère et l'indice de masse corporelle (IMC) sur le sex-ratio. Méthodes : Une étude rétrospective de janvier 2017 à décembre 2023. Les participantes étaient des femmes qui ont eu un TAR et un accouchement réussis à l'unité de conception assistée de Ninewells (NACU) de Dundee et au centre de TAR de l'hôpital universitaire de Lagos, au Nigeria. RESULTATS: Au total, 294 (66,2 %) des dossiers de cas et 150 (33,8 %) ont été évalués respectivement par le NACU et le LUTH. Un plus grand nombre de nourrissons de sexe masculin, 244 (66,8 %), ont accouché à la suite de grossesses conçues avec transfert de stade embryonnaire de blastocyste, par rapport aux nourrissons de sexe féminin, qui s'élevaient à 121 (33,2 %). Concernant le transfert de stades embryonnaires par clivage, 56 (70,9%) étaient en faveur des nouveau-nés de sexe féminin tandis que les mâles représentaient 23 (29,1%). CONCLUSION: L'étude a révélé qu'il y a une augmentation de la proportion de bébés mâles nés suite à certaines techniques de procréation assistée telles que le transfert d'embryons au stade blastocyste et la FIV, tandis qu'un plus grand nombre de bébés femelles sont nés lorsque des embryons au stade clivage ont été transférés ou lorsque l'ICSI a été utilisée comme méthode de fertilisation. MOTS-CLÉS: Ratio de sexes, ICSI, FIV, Blastocyste, Clivage, Race, IMC, Embryon congelé/frais.
Assuntos
Transferência Embrionária , Técnicas de Reprodução Assistida , Razão de Masculinidade , Humanos , Feminino , Masculino , Estudos Retrospectivos , Adulto , Gravidez , Transferência Embrionária/métodos , Fertilização in vitro/métodos , Recém-Nascido , Nigéria , Idade Materna , Índice de Massa Corporal , Injeções de Esperma IntracitoplásmicasRESUMO
Objective: This study aimed to evaluate the effectiveness of oral L-carnitine administration in patients after treatment failure to lay the groundwork for targeted in vivo use. Methods and materials: A total of 515 In Vitro Fertilization (IVF) patients undergoing subsequent cycles were included after applying exclusion criteria. They were divided into a control group of 362 patients and a study group of 153 patients who received oral L-carnitine until oocyte retrieval.140 patients were matched according to maternal age, infertility duration, body mass index (BMI), day three top-quality embryos rate, by propensity score matching (PSM). The study investigated the relationship between L-carnitine treatment and in vivo oocyte maturation, normal fertilization, and subsequent embryo development. Results: Following PSM, initial differences in BMI and Day3 top-quality embryo rate between groups were nullified, we created two comparable cohorts with highly similar characteristics. In the subsequent cycles, the study group showed significant improvements in in vivo oocyte maturation rate at retrieval (p=0.002), normal in vitro fertilization rate (p=0.003), blastocyst formation rate (p=0.003), and usable blastocyst rate compared to controls. Although there was no significant difference in the top-quality embryo rate on Day 3, the study group showed a 10% increase in the upper quartile (55.35% vs. 66.67%). The cumulative clinical pregnancy and live birth rates showed a significant improvement (59.82% vs. 68.42%,p=0.004, 47.41% vs. 59.80%, p=0.002). Furthermore, self-control analysis revealed substantial enhancements (p<0.001) in all outcome measures following L-carnitine administration, resulting in the birth of 74 healthy neonates without congenital anomalies. Conclusion: We theorized that daily oral intake of L-carnitine before oocyte retrieval could boost oocyte quality and embryonic development, thus improving IVF outcomes. Ongoing investigations hold the potential to offer valuable insights into the applications and mechanisms underlying the therapeutic effectiveness of L-carnitine.
Assuntos
Carnitina , Fertilização in vitro , Pontuação de Propensão , Humanos , Carnitina/administração & dosagem , Feminino , Adulto , Fertilização in vitro/métodos , Gravidez , Administração Oral , Taxa de Gravidez , Recuperação de Oócitos/métodos , Infertilidade Feminina/tratamento farmacológico , Doenças Ovarianas/tratamento farmacológico , Resultado do Tratamento , Estudos RetrospectivosRESUMO
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
BACKGROUND: Modifying the maternal immune system is necessary to facilitate embryo implantation. Modifying the immune system can occur in several ways, including maternal exposure to the partner's seminal plasma. Seminal plasma exposure can occur through sexual intercourse. To prove this theory, we investigate the effect of sexual intercourse on the chances of successful in vitro fertilization (IVF) in both fresh and frozen embryo transfer (ET) groups in terms of biochemical and clinical pregnancy. METHODS: This is an observational analytical study with a retrospective cohort study design. This study compared biochemical and clinical pregnancy in patient groups who had sexual intercourse with those who did not have sexual intercourse during the IVF process. This study involved 132 participants. RESULTS: The results of this study reported that there was no significant difference in pregnancy rates between patients who had sex before ET and those who did not have sex before ET. However, patients who experience orgasm during sex show significant rates of biochemical (p = 0.009) and clinical pregnancy (p = 0.027) rates. CONCLUSIONS: Sexual intercourse did not show a significant difference between the groups who had sex before ET and those who did not have sex, but the experience of orgasm every time they had sex recently had a positive impact on reproductive health, especially pregnancy.
Assuntos
Coito , Transferência Embrionária , Fertilização in vitro , Taxa de Gravidez , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Transferência Embrionária/métodos , Adulto , Fertilização in vitro/métodos , Estudos de Coortes , Masculino , Orgasmo , Técnicas de Reprodução AssistidaRESUMO
Purpose: This study aimed to investigate the impact of paternal age > 40 years on clinical pregnancy and perinatal outcomes among patients undergoing in vitro fertilization treatment. Methods: We selected 75 male patients (aged > 40 years) based on predefined inclusion and exclusion criteria. Propensity score matching was performed in a 1:3 ratio, resulting in a control group (aged ≤ 40 years) of 225 individuals. Various statistical tests, including the Mann-Whitney U test, Chi-square test, Fisher's exact test, and binary logistic regression, were used to analyze the association between paternal age and clinical outcomes. Results: We found no statistically significant differences in semen routine parameters, clinical pregnancy outcomes, and perinatal outcomes between paternal aged > 40 and ≤ 40 years. However, in the subgroup analysis, the live birth rate significantly decreased in those aged ≥ 45 compared to those aged 41-42 and 43-44 years (31.25% vs. 69.23% and 65%, respectively; all p < 0.05). Additionally, the clinical pregnancy rate was significantly lower among those aged ≥ 45 than among those aged 41-42 (43.75% vs. 74.36%; p=0.035). Conclusion: Paternal age ≥ 45 years was associated with lower live birth and clinical pregnancy rates.
Assuntos
Transferência Embrionária , Fertilização in vitro , Idade Paterna , Resultado da Gravidez , Taxa de Gravidez , Humanos , Gravidez , Fertilização in vitro/métodos , Feminino , Adulto , Masculino , Transferência Embrionária/métodos , Resultado da Gravidez/epidemiologia , Pessoa de Meia-Idade , Nascido Vivo/epidemiologia , Estudos RetrospectivosRESUMO
Purpose: With the rapid advancement of time-lapse culture and artificial intelligence (AI) technologies for embryo screening, pregnancy rates in assisted reproductive technology (ART) have significantly improved. However, clinical pregnancy rates in fresh cycles remain dependent on the number and type of embryos transferred. The selection of embryos with the highest implantation potential is critical for embryologists and influences transfer strategies in fertility centers. The superiority of AI over traditional morphological scoring for ranking cleavage-stage embryos based on their implantation potential remains controversial. Methods: This retrospective study analyzed 105 fresh embryo transfer cycles at the Centre for Reproductive Medicine from August 2023 to March 2024, following IVF/ICSI treatment at the cleavage stage. All embryos were cultured using time-lapse technology and scored using an automated AI model (iDAScore V2.0). Embryos were categorized into three groups based on the iDAScore V2.0: Group A (8 cells, iDA: 1.0-5.7); Group B (8 cells, iDA: 5.8-8.0); and Group C (>8 cells, iDA: 5.8-8.0). Clinical treatment outcomes, embryonic development, and pregnancy outcomes were analyzed and compared across the groups. Results: Baseline characteristics such as patient age, AMH levels, AFC, and basal sex hormones showed no significant differences among the three groups (p > 0.05). The iDAscores were significantly higher in Group C (7.3 ± 0.5) compared to Group B (6.7 ± 0.5) and the iDAscores were significantly higher in Group B (6.7 ± 0.5) compared to Group A (4.8 ± 1.0) (p < 0.001).The mean number of high-quality embryos was highest in Group C (4.7 ± 3.0), followed by Group B (3.6 ± 1.7) and Group A (2.1 ± 1.2) (p < 0.001). There was no statistical difference (p = 0.392) in the ongoing pregnancy rate for single cleavage-stage transfers between Group B (54.5%, 30/55) and Group A (38.1%, 8/21), although there was a tendency for Group B to be higher. Conclusion: Combining time-lapse culture with AI scoring may enhance ongoing pregnancy rates in single cleavage-stage fresh transfer cycles.
Assuntos
Inteligência Artificial , Técnicas de Cultura Embrionária , Transferência Embrionária , Taxa de Gravidez , Imagem com Lapso de Tempo , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Adulto , Transferência Embrionária/métodos , Técnicas de Cultura Embrionária/métodos , Fase de Clivagem do Zigoto/fisiologia , Fase de Clivagem do Zigoto/citologia , Fertilização in vitro/métodos , Resultado da Gravidez , Desenvolvimento Embrionário/fisiologia , Implantação do EmbriãoRESUMO
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
In this multicenter, non-inferiority, randomized trial, we randomly assigned 992 women undergoing in-vitro fertilization (IVF) with a good prognosis (aged 20-40, ≥3 transferrable cleavage-stage embryos) to strategies of blastocyst-stage (n = 497) or cleavage-stage (n = 495) single embryo transfer. Primary outcome was cumulative live-birth rate after up to three transfers. Secondary outcomes were cumulative live-births after all embryo transfers within 1 year of randomization, pregnancy outcomes, obstetric-perinatal complications, and livebirths outcomes. Live-birth rates were 74.8% in blastocyst-stage group versus 66.3% in cleavage-stage group (relative risk 1.13, 95%CI:1.04-1.22; Pnon-inferiority < 0.001, Psuperiority = 0.003) (1-year cumulative live birth rates of 75.7% versus 68.9%). Blastocyst transfer increased the risk of spontaneous preterm birth (4.6% vs 2.0%; P = 0.02) and neonatal hospitalization >3 days. Among good prognosis women, a strategy of single blastocyst transfer increases cumulative live-birth rates over single cleavage-stage transfer. Blastocyst transfer resulted in higher preterm birth rates. This information should be used to counsel patients on their choice between cleavage-stage and blastocyst-stage transfer (NCT03152643, https://clinicaltrials.gov/study/NCT03152643 ).
Assuntos
Blastocisto , Fertilização in vitro , Nascido Vivo , Humanos , Feminino , Gravidez , Fertilização in vitro/métodos , Adulto , Nascido Vivo/epidemiologia , Prognóstico , Transferência Embrionária/métodos , Resultado da Gravidez/epidemiologia , Transferência de Embrião Único , Fase de Clivagem do Zigoto , Nascimento Prematuro/epidemiologia , Adulto Jovem , Taxa de GravidezRESUMO
Background and Objectives: The anti-Müllerian hormone (AMH) is a crucial biomarker in regulating ovarian follicle development and female fertility. AMH levels predict ovarian responses in in vitro fertilization (IVF) cycles, helping clinicians tailor treatment strategies. This study aims to determine whether thyroid autoimmunity, age, body mass index (BMI), sexual hormone levels, and 25-hydroxyvitamin D levels influence serum AMH in non-polycystic-ovary-syndrome (PCOS) euthyroid women. Materials and Methods: This retrospective cross-sectional study examined 52 female patients at Zygota Fertility Clinic between 2018 and 2022. Women aged 20-45 years with regular menstrual cycles were included, while conditions such as abnormal thyroid-stimulating hormone (TSH) levels, PCOS, and systemic autoimmune diseases were excluded. A number of parameters were measured in the study, including the subjects' age, BMI, 25-hydroxyvitamin D, serum free thyroxine (fT4), TSH, various antibodies, and a range of reproductive hormones. An analysis of the relationships between AMH and other variables was conducted using Spearman's correlation coefficient, and an assessment of the impact of confounding factors on AMH levels was conducted using a multivariable linear regression model. Results: The results revealed significant negative correlations between AMH levels and age (rho: -0.484, p < 0.001) and follicle-stimulating hormone (FSH) (rho: -0.550, p < 0.001), while positive correlations existed between AMH and estradiol (rho: 0.352, p = 0.011) and total testosterone (rho: 0.542, p < 0.001). No significant correlations were found between AMH levels and BMI, LH, or 25-hydroxyvitamin D. Conclusions: In this study, ovarian reserve was influenced by age, estradiol, and total testosterone in non-PCOS euthyroid women undergoing IVF. Conversely, BMI and vitamin D status did not significantly impact AMH levels. In order to better understand and possibly manage ovarian reserve, a holistic approach is absolutely essential, taking into account age, weight, hormonal balance, nutrition, and thyroid health.
Assuntos
Hormônio Antimülleriano , Fertilização in vitro , Vitamina D , Humanos , Feminino , Hormônio Antimülleriano/sangue , Estudos Transversais , Estudos Retrospectivos , Adulto , Fertilização in vitro/métodos , Vitamina D/sangue , Vitamina D/análogos & derivados , Pessoa de Meia-Idade , Índice de Massa Corporal , Tireotropina/sangue , Biomarcadores/sangue , Adulto JovemRESUMO
Reproductive aging is a major cause of fertility decline, attributed to decreased oocyte quantity and developmental potential. A possible cause is aging of the surrounding follicular somatic cells that support oocyte growth and development by providing nutrients and regulatory factors. Here, by creating chimeric follicles, whereby an oocyte from one follicle was transplanted into and cultured within another follicle whose native oocyte was removed, we show that young oocytes cultured in aged follicles exhibited impeded meiotic maturation and developmental potential, whereas aged oocytes cultured within young follicles were significantly improved in rates of maturation, blastocyst formation and live birth after in vitro fertilization and embryo implantation. This rejuvenation of aged oocytes was associated with enhanced interaction with somatic cells, transcriptomic and metabolomic remodeling, improved mitochondrial function and higher fidelity of meiotic chromosome segregation. These findings provide the basis for a future follicular somatic cell-based therapy to treat female infertility.
Assuntos
Oócitos , Folículo Ovariano , Rejuvenescimento , Feminino , Animais , Folículo Ovariano/crescimento & desenvolvimento , Rejuvenescimento/fisiologia , Camundongos , Fertilização in vitro/métodos , Senescência Celular , Meiose , Microambiente Celular , Envelhecimento/fisiologiaRESUMO
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
STUDY QUESTION: Is there a difference in clinical pregnancy rates (CPRs) in good prognosis patients after single embryo transfer (SET) on Day 5, in case of stable culture at 36.6°C or 37.1°C? SUMMARY ANSWER: CPR (with heartbeat at 7 weeks) after blastocyst transfer do not differ after culturing at 36.6°C or 37.1°C. WHAT IS KNOWN ALREADY: Since the beginning of IVF, embryo culture has been performed at 37.0°C; however, the optimal culture temperature remains unknown. Changes in incubator types have led to significant improvements in temperature control. Stable temperature control, i.e. with temperature differences of max. 0.1°C between chambers, is possible in some incubators. A previous prospective pilot study showed that embryo development on Day 5/6 was not affected when embryos were cultured at a stable temperature of 36.6°C or 37.1°C, but culture at 37.1°C resulted in an increased CPR when compared to culture at 36.6°C (74.2% vs 46.4%). STUDY DESIGN, SIZE, DURATION: A prospective randomized controlled trial was performed in a tertiary fertility centre between February 2017 and November 26, 2022. A sample size of 89/89 patients with fresh single embryo transfer (SET) was required to achieve 80% power to detect a difference of 0.22 between group proportions (0.43-0.65) at a significance level of 0.05 using a two-sided z-test with continuity correction. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were recruited on the day of oocyte retrieval based on inclusion criteria with final randomization after denudation once six mature oocytes were present. The primary endpoint was CPR (heartbeat at 7 weeks); secondary endpoints were fertilization rate, blastocyst development, biochemical pregnancy rate, live birth rate (LBR), and cumulative live birth rate (CLBR). MAIN RESULTS AND THE ROLE OF CHANCE: A total of 304 patients were eligible for the study; of these 268 signed the consent, 234 (intention-to-treat) were randomized and 181 (per-protocol) received a SET on Day 5: 90 received culture at 36.6°C and 91 at 37.1°C. Patients were on average 32.4 ± 3.5 versus 32.5 ± 4.2 years old, respectively. No differences were observed in embryological outcomes per cycle between culture at 36.6°C versus 37.1°C: 12.0 ± 3.8 vs 12.1 ± 3.8 COCs retrieved (P = 0.88), 10.0 ± 3.1 versus 9.9 ± 2.9 mature oocytes inseminated (P = 0.68), with a maturation rate of 84.2% (901/1083) versus 83.5% (898/1104) (P = 0.87); and 8.0 ± 3.1 versus 7.9 ± 2.7 normally fertilized oocytes with a fertilization rate of 79.7% (720/901) vs 80.5% (718/898) (P = 0.96), respectively. On average 1.5 ± 1.7 versus 1.4 ± 1.9 (P = 0.25) and 1.1 ± 1.1 versus 0.9 ± 1.0 (P = 0.45) supernumerary blastocysts were vitrified on Day 5 and Day 6, respectively. The utilization rate per fertilized oocyte was 46.1% vs 41.5% (P = 0.14). A SET was performed for 181 patients, leading to a biochemical pregnancy rate of 72.2% (65/90) versus 62.7% (57/91) (P = 0.17), respectively. The CPR per fresh transfer cycle was 51.1% (46/90) versus 48.4% (44/91) [OR (95% CI) 1.11 (0.59-2.08), P = 0.710]. To date, a CLBR of 73.3% (66/90) versus 67.0% (61/91) (P = 0.354) has been observed, respectively. In each group, seven patients without live birth have remaining blastocysts frozen. The CPR for the intention-to-treat groups were 38.3% vs 38.6% [OR (95% CI) 0.98 (0.56-1.73), P = 0.967], respectively, for culture at 36.6°C versus 37.1°C. LIMITATIONS, REASONS FOR CAUTION: Only selected patients with expected good prognosis were eligible for the study. WIDER IMPLICATIONS OF THE FINDINGS: Embryos tend to tolerate small changes in temperature deviations during culture to the blastocyst stage, as demonstrated by their similar implantation potential at two slightly different temperatures. STUDY FUNDING/COMPETING INTEREST(S): There is no funding or conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NCT03548532. TRIAL REGISTRATION DATE: 23 October 2017. DATE OF FIRST PATIENT'S ENROLMENT: 10 November 2017.
Assuntos
Blastocisto , Técnicas de Cultura Embrionária , Fertilização in vitro , Taxa de Gravidez , Temperatura , Humanos , Feminino , Gravidez , Técnicas de Cultura Embrionária/métodos , Adulto , Estudos Prospectivos , Fertilização in vitro/métodos , Transferência de Embrião Único/métodos , Transferência Embrionária/métodosRESUMO
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
AIM: This study aimed to investigate the association between the components of metabolic syndrome (MetS) and reproductive outcomes in women with polycystic ovary syndrome (PCOS) undergoing their first in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) embryo transfer cycle. METHODS: This is a retrospective study that included 720 women with PCOS from January 2018 to December 2021. Anthropometric, biochemical, and reproductive data of the study subjects were collected from electronic medical record. Women with PCOS met <3, 3, and >3 criteria of MetS were classified in group 1, 2, and 3, respectively. RESULTS: The miscarriage rate in women with MetS was significantly higher than that in non-MetS group (23.2% vs. 14.2%, p = 0.03). There was a significant increasing trend in miscarriage rate from group 1 to group 3 (p for trend <0.05). The miscarriage rate in group 3 was significantly higher than that in group 1 (29.3% vs. 14.2%, p < 0.05). Logistic regression analyses showed that women with at least four components of MetS (group 3) were independently associated with a high risk of miscarriage, with the odds ratios and 95% confidence intervals for group 2 and 3 versus group 1 were 1.38 (0.67-2.82) and 2.46 (1.06-5.74), respectively (p for trend = 0.04). CONCLUSIONS: PCOS women accompanied with at least four diagnostic criteria of MetS is independently associated with increased miscarriage rate when undergoing their first IVF or ICSI cycle.
Assuntos
Aborto Espontâneo , Fertilização in vitro , Síndrome Metabólica , Síndrome do Ovário Policístico , Injeções de Esperma Intracitoplásmicas , Humanos , Feminino , Síndrome do Ovário Policístico/complicações , Adulto , Síndrome Metabólica/epidemiologia , Aborto Espontâneo/epidemiologia , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas/estatística & dados numéricos , Gravidez , Fertilização in vitro/estatística & dados numéricos , Fertilização in vitro/métodos , Transferência Embrionária/estatística & dados numéricos , Transferência Embrionária/métodosRESUMO
OBJECTIVES: To evaluate whether embryo transfers at blastocyst stage improve the cumulative live birth rate after oocyte retrieval, including both fresh and frozen-thawed transfers, and whether the risk of obstetric and perinatal complications is increased compared with cleavage stage embryo transfers during in vitro fertilisation (IVF) treatment. DESIGN: Multicentre randomised controlled trial. SETTING: 21 hospitals and clinics in the Netherlands, 18 August 2018 to 17 December 2021. PARTICIPANTS: 1202 women with at least four embryos available on day 2 after oocyte retrieval were randomly assigned to either blastocyst stage embryo transfer (n=603) or cleavage stage embryo transfer (n=599). INTERVENTIONS: In the blastocyst group and cleavage group, embryo transfers were performed on day 5 and day 3, respectively, after oocyte retrieval, followed by cryopreservation of surplus embryos. Analysis was on an intention-to-treat basis, with secondary analyses as per protocol. MAIN OUTCOME MEASURES: The primary outcome was the cumulative live birth rate per oocyte retrieval, including results of all frozen-thawed embryo transfers within a year after randomisation. Secondary outcomes included cumulative rates of pregnancy, pregnancy loss, and live birth after fresh embryo transfer, number of embryo transfers needed, number of frozen embryos, and obstetric and perinatal outcomes. RESULTS: The cumulative live birth rate did not differ between the blastocyst group and cleavage group (58.9% (355 of 603) v 58.4% (350 of 599; risk ratio 1.01, 95% confidence interval (CI) 0.84 to 1.22). The blastocyst group showed a higher live birth rate after fresh embryo transfer (1.26, 1.00 to 1.58), lower cumulative pregnancy loss rate (0.68, 0.51 to 0.89), and lower mean number of embryo transfers needed to result in a live birth (1.55 v 1.82; P<0.001). The incidence of moderate preterm birth (32 to <37 weeks) in singletons was higher in the blastocyst group (1.87, 1.05 to 3.34). CONCLUSION: Blastocyst stage embryo transfers resulted in a similar cumulative live birth rate to cleavage stage embryo transfers in women with at least four embryos available during IVF treatment. TRIAL REGISTRATION: International Clinical Trial Registry Platform NTR7034.
Assuntos
Blastocisto , Transferência Embrionária , Fertilização in vitro , Nascido Vivo , Humanos , Feminino , Transferência Embrionária/métodos , Gravidez , Fertilização in vitro/métodos , Adulto , Nascido Vivo/epidemiologia , Criopreservação , Recuperação de Oócitos/métodos , Fase de Clivagem do Zigoto , Coeficiente de Natalidade , Países Baixos , Prognóstico , Taxa de GravidezRESUMO
AIM: To assess the efficacy of intratesticular injection of autologous platelet-rich plasma (PRP) in men with non-obstructive azoospermia (NOA) and a history of failed microdissection-testicular sperm extraction (mTESE) procedures. METHODS: A prospective case series of a cohort study was conducted involving couples diagnosed with NOA. Patients with at least one failed mTESE procedure were included. Intratesticular PRP injection was performed using a standardized protocol. Follow-up assessments included sperm analysis, hormonal evaluation, and in vitro fertilization (IVF) outcomes. RESULTS: Data from 177 men with NOA were analyzed, with 135 patients meeting eligibility criteria. PRP treatment resulted in positive sperm retrieval rates of 27.5% in patients with one prior failed mTESE procedure and 16.4% in patients with two or more failed attempts. IVF outcomes showed fertilization rates of 86.4% and 100.0% in respective groups, with pregnancy rates of 36.8% and 22.2% per embryo transfer. Histopathological examination post-mTESE revealed varied patterns, including Sertoli cell-only syndrome and maturation arrest. CONCLUSIONS: Intratesticular PRP injection shows promise as a potential therapeutic approach for NOA patients with prior failed mTESE procedures, demonstrating improved sperm retrieval rates and favorable IVF outcomes. Further randomized controlled trials are warranted to validate these findings and refine the technique's efficacy in male infertility management to answer the question of whether PRP could significantly improve the second attempt retrieval rate.
Assuntos
Azoospermia , Fertilização in vitro , Plasma Rico em Plaquetas , Recuperação Espermática , Humanos , Azoospermia/terapia , Masculino , Adulto , Feminino , Fertilização in vitro/métodos , Gravidez , Estudos Prospectivos , Taxa de Gravidez , Testículo , Resultado do TratamentoRESUMO
BACKGROUND: Data sciences and artificial intelligence are becoming encouraging tools in assisted reproduction, favored by time-lapse technology incubators. Our objective is to analyze, compare and identify the most predictive machine learning algorithm developed using a known implantation database of embryos transferred in our egg donation program, including morphokinetic and morphological variables, and recognize the most predictive embryo parameters in order to enhance IVF treatments clinical outcomes. METHODS: Multicenter retrospective cohort study carried out in 378 egg donor recipients who performed a fresh single embryo transfer during 2021. All treatments were performed by Intracytoplasmic Sperm Injection, using fresh or frozen oocytes. The embryos were cultured in Geri® time-lapse incubators until transfer on day 5. The embryonic morphokinetic events of 378 blastocysts with known implantation and live birth were analyzed. Classical statistical analysis (binary logistic regression) and 10 machine learning algorithms were applied including Multi-Layer Perceptron, Support Vector Machines, k-Nearest Neighbor, Cart and C0.5 Classification Trees, Random Forest (RF), AdaBoost Classification Trees, Stochastic Gradient boost, Bagged CART and eXtrem Gradient Boosting. These algorithms were developed and optimized by maximizing the area under the curve. RESULTS: The Random Forest emerged as the most predictive algorithm for implantation (area under the curve, AUC = 0.725, IC 95% [0.6232-0826]). Overall, implantation and miscarriage rates stood at 56.08% and 18.39%, respectively. Overall live birth rate was 41.26%. Significant disparities were observed regarding time to hatching out of the zona pellucida (p = 0.039). The Random Forest algorithm demonstrated good predictive capabilities for live birth (AUC = 0.689, IC 95% [0.5821-0.7921]), but the AdaBoost classification trees proved to be the most predictive model for live birth (AUC = 0.749, IC 95% [0.6522-0.8452]). Other important variables with substantial predictive weight for implantation and live birth were duration of visible pronuclei (DESAPPN-APPN), synchronization of cleavage patterns (T8-T5), duration of compaction (TM-TiCOM), duration of compaction until first sign of cavitation (TiCAV-TM) and time to early compaction (TiCOM). CONCLUSIONS: This study highlights Random Forest and AdaBoost as the most effective machine learning models in our Known Implantation and Live Birth Database from our egg donation program. Notably, time to blastocyst hatching out of the zona pellucida emerged as a highly reliable parameter significantly influencing our implantation machine learning predictive models. Processes involving syngamy, genomic imprinting during embryo cleavage, and embryo compaction are also influential and could be crucial for implantation and live birth outcomes.
Assuntos
Blastocisto , Implantação do Embrião , Aprendizado de Máquina , Doação de Oócitos , Humanos , Feminino , Estudos Retrospectivos , Doação de Oócitos/métodos , Gravidez , Adulto , Blastocisto/fisiologia , Blastocisto/citologia , Implantação do Embrião/fisiologia , Taxa de Gravidez , Fertilização in vitro/métodos , Injeções de Esperma Intracitoplásmicas/métodos , Transferência Embrionária/métodosRESUMO
The utilization of electroporation for delivering CRISPR/Cas9 system components has enabled efficient gene editing in mammalian zygotes, facilitating the development of genome-edited animals. In this study, our research focused on targeting the ACTG1 and MSTN genes in sheep, revealing a threshold phenomenon in electroporation with a voltage tolerance in sheep in vitro fertilization (IVF) zygotes. Various poring voltages near 40 V and pulse durations were examined for electroporating sheep zygotes. The study concluded that stronger electric fields required shorter pulse durations to achieve the optimal conditions for high gene mutation rates and reasonable blastocyst development. This investigation also assessed the quality of Cas9/sgRNA ribonucleoprotein complexes (Cas9 RNPs) and their influence on genome editing efficiency in sheep early embryos. It was highlighted that pre-complexation of Cas9 proteins with single-guide RNA (sgRNA) before electroporation was essential for achieving a high mutation rate. The use of suitable electroporation parameters for sheep IVF zygotes led to significantly high mutation rates and heterozygote ratios. By delivering Cas9 RNPs and single-stranded oligodeoxynucleotides (ssODNs) to zygotes through electroporation, targeting the MSTN (Myostatin) gene, a knock-in efficiency of 26% was achieved. The successful generation of MSTN-modified lambs was demonstrated by delivering Cas9 RNPs into IVF zygotes via electroporation.