Spontaneous Live Birth Research Articles

True empty follicle syndrome is a subtype of oocyte maturation abnormalities.

To review the outcomes of in vitro maturation (IVM) and in vitro fertilization (IVF) in women with empty follicle syndrome (EFS). The study evaluated the genetic underpinnings of EFS by analyzing mutations. This retrospective case series involving 17 women with EFS over at least 2 IVF cycles was conducted. The study also employed whole-exome sequencing to analyze the genetic mutations. The treatment approaches included letrozole-primed IVM, follicle-stimulating hormone (FSH)-human chorionic gonadotrophin (hCG)-primed IVM, and conventional IVF. The average female age was 31.5±4.6 years, and the duration of infertility was 7.3±3.5 years. Four patients underwent IVF. IVM oocyte collections yielded oocytes in 12 of 13 subjects. Of these, 75% (9/12) yielded MII oocytes after 48 h of IVM media incubation. Six subjects had fertilized embryos, resulting in a 40.9% intracytoplasmic sperm injection (ICSI) fertilization rate (9 embryos/22 MII oocytes). Genetic analysis revealed mutations in seven patients. This study demonstrated the partial efficacy of letrozole-primed IVM plus growth hormone and FSH-hCG primed IVM protocols. No pregnancies or live births were recorded after IVM. One ongoing pregnancy post-IVF and one spontaneous live birth were observed. Inter-cycle variabilities were observed in women with oocyte maturation abnormalities (OMAs). Almost all patients with EFS had oocytes collected during IVM following IVF. These oocytes have limited potential for maturation, fertilization, and live birth, as demonstrated by the low rates observed after IVM culture and ICSI. These conditions are observed in OMAs due to defects in the oocyte machinery. The proposed flowchart provides a comprehensive classification approach for various forms of EFS.

Female fertility preservation for family planning: a position statement of the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR).

This position statement by the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR) aims to establish an optimal framework for fertility preservation outside the standard before oncological therapies. Key topics include the role of fertility units in comprehensive fertility assessment, factors impacting ovarian potential, available preservation methods, and appropriate criteria for offering such interventions. The SIFES-MR writing group comprises Italian reproductive physicians, embryologists, and scientists. The consensus emerged after a six-month period of meetings, including extensive literature review, dialogue among authors and input from society members. Final approval was granted by the SIFES-MR governing council. Fertility counselling transitions from urgent to long-term care, emphasizing family planning. Age, along with ovarian reserve markers, is the primary predictor of female fertility. Various factors, including gynecological conditions, autoimmune disorders, and prior gonadotoxic therapies, may impact ovarian reserve. Oocyte cryopreservation should be the preferred method. Women 30-34 years old and 35-39 years old, without known pathologies impacting the ovarian reserve, should cryopreserve at least 12-13 and 15-20 oocytes to achieve the same chance of a spontaneous live birth they would have if they tried to conceive at the age of cryopreservation (63% and 52%, respectively in the two age groups). Optimal fertility counselling necessitates a long-term approach, that nurtures an understanding of fertility, facilitates timely evaluation of factors that may affect fertility, and explores fertility preservation choices at opportune intervals.

Association of preoperative Enzian score with postoperative fertility in patients with deep pelvic endometriosis

IntroductionEndometriosis is a chronic inflammatory disease with a negative impact on fertility. The Enzian classification provides a precise description of deep pelvic endometriotic lesions, especially in the retroperitoneal area, from preoperative pelvic MRI scans. However, it is not known if it is correlated with postoperative fertility. Study objectiveTo determine if there is an association between the preoperative Enzian score and postoperative fertility after deep pelvic endometriosis surgery. DesignWe conducted a descriptive, retrospective study using information from the ENDOREN database. SettingThis was a retrospective study at the Department of Obstetrics and Gynecology at Rennes University Hospital (France) from January 2013 to May 2019 Patients and interventionsWe used information from the ENDOREN database that included all women who underwent surgery for deep endometriosis and wish to conceive. This surgery was intended in a view to achieve a complete removal of endometriosis. MeasurementsThe Enzian score was calculated from preoperative MRI scans, and total, spontaneous, and after In Vitro fertilization (IVF) live births and pregnancies outcomes were collected from the patients'computerized medical records. Univariate and multivariate analysis was performed. ResultsSixty-eight patients were included. The live-birth rate was 35% (24/68). According to the Enzian classification, 25 patients (35%) were classified in compartment A, 64 patients (94%) in compartment B, and 27 (40%) in compartment C. In multivariate analysis, positive predictor of live birth was single Enzian B score (OR=4.7[1.21; 18.81], p = 0.03), negative predictors were uterine adenomyosis and a history of endometriosis surgery. In multivariate analysis, positive predictor of spontaneous live birth was EFI score ≥7 (OR =22.434; CI [1.138; 442.190]). In multivariate analysis, positive predictor was Enzian A score (OR=15.9[2.2; 114.7], p = 0.006), and negative predictors was uterine adenomyosis and Enzian B score (OR=0.01[0; 0.495], p = 0.02) for live birth after IVF. ConclusionThe present retrospective study cannot strongly conclude about fertility and correlation with Enzian score because the groups are too small. However, it seems that when solely the compartment B is involved by endometriosis, complete full removal of endometriosis leads to better post-operative live births results. Other studies must be done to determine if Enzian classification based on preoperative pelvic MRI could be clinical value in the decision-making strategy for managing infertile patients with deep pelvic endometriosis.

P–330 Live birth after ART in patients with treated endometriosis versus those without endometriosis at laparoscopy

Abstract Study question Is endometriosis related to worse outcome of assisted reproductive techniques (ART)? Summary answer Cumulative incidence of live birth in patients with and without endometriosis at laparoscopy was similar, although deep endometriosis and adenomyosis were negative prognostic factors. What is known already Whether endometriosis has a negative impact on the outcome of ART is still a matter of debate. Most published data report on one fresh cycle only, usually without taking frozen embryos into account. Further, a large heterogeneity in study population has been acknowledged by several meta-analyses, as in the control groups endometriosis was not always excluded by laparoscopy, and in case of endometriosis the prior treatment history was variable or unclear. Study design, size, duration Retrospective longitudinal cohort study of 1462 patients (779 with laparoscopically treated endometriosis of any rASRM stage, and 683 without endometriosis at laparoscopy) undergoing ART treatment between July 2003 and December 2014. Primary outcome studied was time to ART live birth. Secondary outcomes include -amongst others- number of cycles needed per ART live birth, time to ART or spontaneous live birth, cycle cancellation rate, and pregnancy outcomes like miscarriage and ectopic pregnancy, and per cycle analyses. Participants/materials, setting, methods All patients with a history of laparoscopy prior to the start of their first ART were included for analysis. The ART was performed in a tertiary referral center of a large University Hospital. Primary outcome studied was the time from initiation of the first ART cycle to delivery of the first live born. Survival analysis was conducted using cumulative incidence functions and cause-specific hazards regression. Main results and the role of chance The study included 1462 patients who initiated 4537 ART cycles, of which 3672 (81%) fresh and 857 (19%) frozen cycles. The unadjusted hazard ratio (HR) of live birth was 1.01 (95% CI 0.88–1.16). After adjustment for potential confounders (age, maternal BMI, maternal smoking, secondary infertility, duration of infertility, anovulation, reduced ovarian reserve, tubal factor, male factor and therapy started before 2007) the HR was 0.99 (95% CI 0.86–1.14). Within the endometriosis population (n = 779), covariate-adjusted analyses suggested that presence of adenomyosis (HR = 0.54; 95% CI 0.34–0.86) and a history of deep endometriosis (HR = 0.74 – 95% CI 0.58–0.94) were associated with a lower cumulative incidence of live birth. In contrast, there was little support of an association with diagnosis of stage III/IV (HR = 1.15; 95% CI 0.84–1.59) or a history of ovarian endometriosis (HR = 0.97; 95% CI 0.72–1.30). Beside the effect of the different variables directly linked to endometriosis, maternal BMI (HR = 0.80; 95%CI 0.71–0.91) and smoking (HR = 0.69; 95%CI 0.52–0.92) also negatively affected live birth delivery rate per patient. Limitations, reasons for caution Practices and success rates of ART may have changed during the 11-year recruitment period. Restricting to women who underwent laparoscopy, while providing evidence of the presence or absence of endometriosis, may have induced selection bias. However, the advantage of this time period, was the high rate of pre-ART laparoscopy (+/–50%). Wider implications of the findings: As deep endometriosis and adenomyosis represent negative prognostic factors within the endometriosis population, future studies should focus on optimalisation of ART in these subgroups. Trial registration number S57393

Cost of fertility treatment and live birth outcome in women of different ages and BMI.

What is the impact of different age and BMI groups on total investigation and treatment costs in women attending a secondary/tertiary care fertility clinic? Women in their early to mid-30s and women with normal BMI had higher cumulative investigation and treatment costs, but also higher probability of live birth. Female age and BMI have been used as criteria for rationing publically funded fertility treatments. Population-based data on the costs of investigating and treating infertility are lacking. A retrospective cohort study of 2463 women was conducted in a single secondary/tertiary care fertility clinic in Aberdeen, Scotland from 1998 to 2008. Participants included all women living in a defined geographical area referred from primary care to a specialized fertility clinic over an 11-year period. Women were followed up for 5 years or until live birth if this occurred sooner. Mean discounted cumulative National Health Service costs (expressed in 2010/2011 GBP) of fertility investigations, treatments (including all types of assisted reproduction), and pregnancy (including delivery episode) and neonatal admissions were calculated and summarized by age (≤ 30, 31-35, 36-40, >40 years) and BMI groupings (<18.50, 18.50-24.99 (normal BMI), 25.00-29.99, 30.00-34.99, ≥ 35.00 kg/m(2)). Further multivariate modelling was carried out to estimate the impact of age and BMI on investigation and treatment costs and live birth outcome, adjusting for covariates predictive of the treatment pathway and live birth. Of the 2463 women referred, 1258 (51.1%) had a live birth within 5 years, with 694 (55.1%) of these being natural conceptions. The live birth rate was highest among women in the youngest age group (64.3%), and lowest in those aged >40 years (13.4%). Overall live birth rates were generally lower in women with BMI >30 kg/m(2). The total costs of investigations were generally highest among women younger than 30 years (£491 in those with normal BMI), whilst treatment costs tended to be higher in 31-35 year olds (£1,840 in those with normal BMI). Multivariate modelling predicted a cost increase associated with treatment which was highest among women in the lowest BMI group (across all ages), and also highest among women aged 31-35 years. The increase in the predicted probability of live birth with exposure to treatment was consistent across age and BMI categories (∼ 10%), except in the oldest age group where a slightly smaller increase in the probability of live birth was observed. The ratio of increased costs to the increased probability of live birth in women who were treated increased markedly in women over the age of 40 years, but tended to fall as BMI increased within all age groups. Our results, based on retrospective observational data from a single centre, have limited generalizability and are not free from clinician and clinic selection bias which can influence the choice of treatments as well as their costs. Spontaneous live birth rates were particularly high in younger women with unexplained infertility, suggesting that expectant management is a reasonable option in this group. The policy of not over-investigating older women and offering early treatment where appropriate still incurred the highest costs per additional live birth associated with treatment, owing to the lower probability of treatment success. The increased additional cost for each live birth associated with treatment for women with decreasing BMI across all age groups, suggests that it may be possible to identify a more targeted approach to treatment. This study was partly funded by an NHS endowment grant (Grant Number 12/48) and D.J.M. by a Chief Scientist Office Postdoctoral Fellowship (Ref PDF/12/06). There are no conflicts of interest to declare.

Spontaneous conceptions following successful ART are not associated with premature referral

What is the rate of spontaneous live births after successful IVF treatment in a cost-free environment, and were couples who achieved a spontaneous live birth referred prematurely? Despite unlimited IVF treatments offered free of charge, the spontaneous live birth rate following successful IVF remained unchanged compared with that cited in previous literature. Couples were not referred prematurely to IVF before fully utilizing other less invasive treatments. A significant number of infertile couples, who achieve their first live birth through assisted reproductive technology (ART), subsequently achieve a second live birth spontaneously. As IVF has become more widely available, it is used in less severe cases of infertility, perhaps explaining a rise in the subsequent spontaneous live birth rate after successful treatments. This retrospective cohort study was performed at a university-based tertiary medical center. The study population included women aged <35 years, with primary infertility, referred for their first IVF treatment to the Sheba Medical Center IVF unit between 2001 and 2002 and followed up for 7 years. The primary outcome was spontaneous live birth rate following successful ART. Relevant data were obtained from the patient files and supplemented by a standardized telephone questionnaire. Of the 171 couples who met the study inclusion criteria, 6 refused to participate in the questionnaire and 31 couples were lost to follow-up. Of the 134 couples who participated, 109 achieved a first live birth with ART. After achieving their first live birth with ART, seven couples who began using contraception or separated or divorced were excluded. Of 102 couples who continued unprotected intercourse after successful ART, 22 subsequently achieved their second live birth spontaneously (21.6%). The women who achieved a second birth spontaneously were not referred earlier to IVF, and actually performed a higher number of ovulation induction cycles before initiating IVF, compared with women who did not conceive spontaneously. This is a retrospective cohort study, and findings should be reaffirmed with a larger prospective randomized study comparing retreatment to achieve a second pregnancy with attempting to conceive spontaneously. Our data suggests that young patients (<35 years), who previously conceived with IVF, without utilizing ICSI and with no known tubal pathology, should consider attempting to conceive spontaneously. No funding was obtained for this study and the authors have no competing interests.

Development of clinical priority access criteria for assisted reproduction and its evaluation on 1386 infertile couples in New Zealand

In New Zealand ranking patients for elective, publicly funded procedures uses clinical priority access criteria (CPAC). A CPAC to prioritize patients seeking assisted reproductive technology (ART) was developed in 1997 and implemented nationwide in 2000. This study describes the development of the ART CPAC tool and its evaluation on 1386 couples referred to a single tertiary service from 1998 to 2005. A total of 48 health professionals and consumers assisted in criteria development. A score between 0 and 100 points was calculated for each couple and those who reached ≥65 points were eligible for publicly funded ART. Couples beneath the treatment threshold were placed on active review; the review being the date the score was calculated to reach the treatment threshold. Couples who would never be eligible or who were on active review were offered private treatment. Treatments and outcomes (spontaneous and treatment dependent live birth pregnancies) were used to evaluate the criteria. Three social criteria (duration infertility, number of children and sterilization status) and two objective criteria (diagnosis and female age) formed the priority score. Of the evaluated couples, 643 (46%) were eligible within 1 year of referral (Group 1), 451 (33%) >1-5 years from referral (Group 2) and 292 (21%) couples were never eligible (Group 3). The predominant ART was IVF. A total of 480 couples had at least one IVF treatment with 404 (84%) having publicly funded treatment. A total of 762 (55%) women gave birth, 473 from treatment and 289 spontaneously. Group 1 had more pregnancies from treatment while Group 2 had most pregnancies overall being mainly from spontaneous pregnancies. Compared with Group 3 cases the hazard ratio using time to spontaneous live birth pregnancy for Group 1 couples was significantly lower, 0.51 (95% confidence interval 0.36-0.74) and for Group 2 cases significantly higher, 1.86, (1.35-2.58). Treatments using ART were evaluated for the three eligibility groups, with the never eligible divided into women age <40 (Group 3a) and woman age ≥40 at referral (Group 3b). Compared with Group 1 cases the hazard ratio to treatment dependent live birth pregnancy was similar for Groups 2 and 3a but significantly lower for Group 3b (0.37, 0.14-0.90). The clinical priority access score was able to discriminate between the chance of pregnancy with and without treatment and those offered and not offered treatment. The CPAC is a useful model for informing the allocation of public funding for ART in other countries.

O6-5.6 Spontaneous live birth after in vitro fertilisation treatment: frequency and associated factors

IntroductionSpontaneous live births (SLB) after in vitro fertilisation (IVF) treatment are not unusual, but reported SLB rates vary widely and little is known of their associated factors. Our objective was...

Predicting Live Birth, Preterm Delivery, and Low Birth Weight in Infants Born from In Vitro Fertilisation: A Prospective Study of 144,018 Treatment Cycles

The extent to which baseline couple characteristics affect the probability of live birth and adverse perinatal outcomes after assisted conception is unknown. We utilised the Human Fertilisation and Embryology Authority database to examine the predictors of live birth in all in vitro fertilisation (IVF) cycles undertaken in the UK between 2003 and 2007 (n = 144,018). We examined the potential clinical utility of a validated model that pre-dated the introduction of intracytoplasmic sperm injection (ICSI) as compared to a novel model. For those treatment cycles that resulted in a live singleton birth (n = 24,226), we determined the associates of potential risk factors with preterm birth, low birth weight, and macrosomia. The overall rate of at least one live birth was 23.4 per 100 cycles (95% confidence interval [CI] 23.2-23.7). In multivariable models the odds of at least one live birth decreased with increasing maternal age, increasing duration of infertility, a greater number of previously unsuccessful IVF treatments, use of own oocytes, necessity for a second or third treatment cycle, or if it was not unexplained infertility. The association of own versus donor oocyte with reduced odds of live birth strengthened with increasing age of the mother. A previous IVF live birth increased the odds of future success (OR 1.58, 95% CI 1.46-1.71) more than that of a previous spontaneous live birth (OR 1.19, 95% CI 0.99-1.24); p-value for difference in estimate <0.001. Use of ICSI increased the odds of live birth, and male causes of infertility were associated with reduced odds of live birth only in couples who had not received ICSI. Prediction of live birth was feasible with moderate discrimination and excellent calibration; calibration was markedly improved in the novel compared to the established model. Preterm birth and low birth weight were increased if oocyte donation was required and ICSI was not used. Risk of macrosomia increased with advancing maternal age and a history of previous live births. Infertility due to cervical problems was associated with increased odds of all three outcomes-preterm birth, low birth weight, and macrosomia. Pending external validation, our results show that couple- and treatment-specific factors can be used to provide infertile couples with an accurate assessment of whether they have low or high risk of a successful outcome following IVF.

Predicting live birth, preterm and low birth weight infant after in-vitro fertilization: a prospective study of 144,018 treatment cycles

Background The extent to which baseline couple characteristics affect the probability of live birth and adverse perinatal outcomes after assisted conception is unknown. Methods and Findings We utilised the Human Fertilisation and Embryology Authority database to examine the predictors of live birth in all in vitro fertilisation (IVF) cycles undertaken in the UK between 2003 and 2007 (n = 144,018). We examined the potential clinical utility of a validated model that pre-dated the introduction of intracytoplasmic sperm injection (ICSI) as compared to a novel model. For those treatment cycles that resulted in a live singleton birth (n = 24,226), we determined the associates of potential risk factors with preterm birth, low birth weight, and macrosomia. The overall rate of at least one live birth was 23.4 per 100 cycles (95% confidence interval [CI] 23.2–23.7). In multivariable models the odds of at least one live birth decreased with increasing maternal age, increasing duration of infertility, a greater number of previously unsuccessful IVF treatments, use of own oocytes, necessity for a second or third treatment cycle, or if it was not unexplained infertility. The association of own versus donor oocyte with reduced odds of live birth strengthened with increasing age of the mother. A previous IVF live birth increased the odds of future success (OR 1.58, 95% CI 1.46–1.71) more than that of a previous spontaneous live birth (OR 1.19, 95% CI 0.99–1.24); p-value for difference in estimate <0.001. Use of ICSI increased the odds of live birth, and male causes of infertility were associated with reduced odds of live birth only in couples who had not received ICSI. Prediction of live birth was feasible with moderate discrimination and excellent calibration; calibration was markedly improved in the novel compared to the established model. Preterm birth and low birth weight were increased if oocyte donation was required and ICSI was not used. Risk of macrosomia increased with advancing maternal age and a history of previous live births. Infertility due to cervical problems was associated with increased odds of all three outcomes—preterm birth, low birth weight, and macrosomia. Conclusions Pending external validation, our results show that couple- and treatment-specific factors can be used to provide infertile couples with an accurate assessment of whether they have low or high risk of a successful outcome following IVF.

Spontaneous Live Birth with a Maternal History of Intravenous Use of Pentazocine and Tripelennamine (T's and Blues)

A 24-year-old black female presented a live birth of six-months gestation. The 700-g neonate survived for 11 h. After toxicology revealed the presence of pentazocine and tripelennamine (T's and Blues), the mother admitted to using this combination intravenously 9 h previous to admission. Concentrations of pentazocine and tripelennamine were simultaneously determined by gas-liquid chromatography (GLC) combined with nitrogen selective detection. Analyses were performed on a 3% OV-101 column, with the added internal standard, dexbrompheniramine. Both pentazocine and tripelennamine were qualitatively confirmed by their electron impact mass spectra. Concentrations of pentazocine and tripelennamine in various fluids and tissues were determined.