Proficiency in oocyte retrieval assessed by the learning curve cumulative summation test.

The number of procedures required for a trainee to reach proficiency in oocyte retrieval and the criteria applied to define performance are not well defined. To evaluate the learning curve of oocyte retrieval, this study prospectively evaluated three trainees over 6 months. Oocyte retrieval was monitored by the learning curve-cumulative summation test (LC-CUSUM), a specific statistical tool designed to indicate when a predefined level of performance is reached. Oocytes were retrieved from one ovary by the trainee and from the second ovary by a senior operator in a randomized manner. The main outcome measure was the ratio of oocytes collected and follicles aspirated. A trainee's ratio of ≥ 80% of the senior operator's defined success. From 17 to >50 procedures were necessary for the trainees to reach the predefined level of performance. Cumulative summation tests implemented after the learning phase confirmed that performance was maintained. The present study confirms the large variability in acquiring proficiency for surgical procedures. It provides an exportable model for a quantitative tailored monitoring of the learning curve and for continuous monitoring of performance in oocyte retrieval.

Comparison of embryo morphokinetics after in vitro fertilization-intracytoplasmic sperm injection in smoking and nonsmoking women.

OBJECTIVE: To evaluate the impact of female smoking on early embryo development in vitro using a time-lapse system. DESIGN: Retrospective analysis of prospectively collected database. SETTING: Assisted reproductive technology (ART) program. PATIENT(S): A total of 135 infertile couples undergoing IVF-intracytoplasmic sperm injection (ICSI) cycle. INTERVENTION(S): Embryo culture in a time-lapse incubator (Embryoscope, Unisense Fertilitech). MAIN OUTCOME MEASURE(S): Embryo morphokinetic parameters. RESULT(S): Of 135 women, 139 and 729 oocytes were cultured in 23 smokers and 112 nonsmokers, respectively. Basal characteristics and ovarian stimulation parameters were comparable in both groups. Serum antimüllerian hormone level and antral follicle count were significantly lower in smokers than in nonsmokers. Conventional embryologic parameters were comparable in both groups, but time-lapse analysis showed that most cleavage events occurred significantly later in smokers than in nonsmokers, leading to poor cycle outcome in smokers. CONCLUSION(S): Female smoking impairs early embryo development, as reflected by time-lapse analysis. This might contribute to the dramatic decrease in pregnancy rates (PRs) in smokers undergoing IVF. Time lapse is a useful tool for the identification of deleterious components impairing early embryo development.

Prospective, randomized comparison between pulsatile GnRH therapy and combined gonadotropin (FSH+LH) treatment for ovulation induction in women with hypothalamic amenorrhea and underlying polycystic ovary syndrome.

OBJECTIVE(S): To compare the efficacy of pulsatile GnRH therapy versus combined gonadotropins for ovulation induction in women with both hypothalamic amenorrhoea and polycystic ovarian syndrome (HA/PCOS) according to their current hypothalamic status. STUDY DESIGN: This single-centre, prospective, randomized study was conducted in the Nantes University Hospital, France. Thirty consecutive patients were treated for ovulation induction with either pulsatile GnRH therapy or combined gonadotropins (rFSH+rLH). Frequency of adequate ovarian response (mono- or bi-follicular) and clinical pregnancy rate were then compared between both groups. RESULTS: Ovarian response was similar in both groups with comparable frequency of adequate ovarian response (73% vs 60%), but the clinical pregnancy rate was significantly higher in the pulsatile GnRH therapy group than in the combined gonadotropin group (46% vs 0%). CONCLUSIONS: HA/PCOS is a specific subgroup of infertile women. Pulsatile GnRH therapy is an effective and safe method of ovulation induction that can be used successfully in these patients.

Ovarian reserve and in vitro fertilization cycles outcome according to women smoking status and stimulation regimen.

PURPOSE: Smoking is known to be deleterious on female fertility and in vitro fertilization (IVF) outcome, probably partly through ovarian reserve alteration. Recently, anti-Müllerian hormone (AMH) and antral follicle count (AFC) have been shown to be the most accurate ovarian reserve markers. Here, we compared ovarian reserve markers in women undergoing IVF according to smoking status and stimulation regimen. METHODS: AFC, AMH, basal FSH, LH and estradiol, and IVF outcome were compared in 277 women undergoing IVF. Smoking status and ovarian stimulation protocol (i.e. agonists or antagonists) were recorded. RESULTS: Active smoking women had lower AMH and modified follicles' size repartition in AFC compared to non-smokers. They also experienced poorer IVF outcome with decreased ovarian response and lower pregnancy rate. This remained true in both antagonist and agonist stimulation protocol groups. CONCLUSION: Active smoking in infertile women is associated with ovarian reserve alteration, as reflected by AFC modification and decreased serum AMH, and leads to poor prognosis in ART cycles, whatever the stimulation protocol used. Infertile women should be strongly discouraged from smoking before they start IVF cycles.

Prolonging GnRH-agonist to achieve ovarian suppression does not compromise the results of a long protocol.

OBJECTIVES: In the long gonadotropin-releasing hormone agonist (GnRHa) protocols, stimulation is delayed until complete pituitary-ovarian suppression has been achieved, which usually takes a minimum of 10 days. In women who do not achieve timely suppression we set out to evaluate if prolonging GnRHa affects the results of the IVF process. STUDY DESIGN: We analyzed cycle and pregnancy outcome in 506 consecutive women undergoing IVF-ET after a standardized long GnRHa protocol, according to the time required to achieve ovarian suppression (i.e. estradiol< 40 pg/mL and no follicle >6mm at ultrasound). RESULTS: Suppression was obtained after 14 GnRHa days in 383 (75.70%) women (Group 1) and 123 (24.30%) women (Group 2) required a mean ± SD (range) of 10 ± 4 (7-28) additional days to achieve complete suppression. Both groups were comparable for baseline clinical and biological characteristics. The rate of cancelled cycles due to poor ovarian response, the number of the oocytes retrieved, fertilization rates, the number and quality of the embryos cultured and transferred were similar in both groups, as well as the pregnancy, implantation and live birth rates. In Group 2, receiver-operator characteristics analysis showed that the probability of pregnancy was not related to the duration of GnRHa treatment. CONCLUSIONS: In a standardized long GnRHa protocol, prolonging desensitization to achieve complete ovarian suppression does not affect the outcome.

Predictive factors of healthy term birth after single blastocyst transfer.

BACKGROUND: Blastocyst culture and elective single embryo transfer programmes are increasingly used to reduce multiple pregnancies after IVF. To optimize the results, there is a need to better select embryos, to implement efficient cryopreservation programmes and to refine selection criteria. In the present study, we set out to identify relevant clinical predictors of healthy term birth (HTB) after single blastocyst transfer (SBT). DESIGN: analysis of prospectively collected database. SETTING: University IVF centre in Nantes, France. In 872 infertile women undergoing their first IVF cycle with SBT between January 2007 and December 2008, multivariable analysis and logistic regression were used to identify predictive factors of HTB, i.e. delivery of a live born term singleton of ≥ 2500 g, surviving at least 28 days with no reported congenital anomaly. RESULTS: Of 304 deliveries, there were 16 twin pairs (5.5%) and no high order deliveries. The rate of HTB was 266/872 (30.5%). Univariate analysis showed that the probability of HTB was significantly higher in women under 35 years [odds ratio (OR):1.75, 0.95 confidence interval (CI): 1.2-2.5, P = 0.001], in women with a BMI < 30 kg/m² (OR: 3.0, 0.95 CI: 1.5-5.9, P = 0.001), in non-smoking women (OR: 2.2, 0.95 CI: 1.5-3.2, P < 0.0001), and after Day 5 compared with after Day 6 transfer (OR: 2.65, 0.95 CI: 1.8-3.8, P < 0.0001). Multivariable analysis showed that BMI, smoking and day of embryo transfer were independent predictors of HTB, regardless of female age. CONCLUSIONS: After SBT, female obesity and smoking reduce the chance of HTB, independent of female age. Day 6 transfer should be avoided.

Polymorphisms in MTHFR and MTRR genes associated with blood plasma homocysteine concentration and sperm counts.

OBJECTIVE: To investigate the relationship between MTHFR and MTRR genetic variants with respect to both blood plasma homocysteine concentration and sperm counts. DESIGN: Polymerase chain reaction followed by specific enzymatic digestion to determine the genotype of the individuals and blood plasma homocysteine quantification by high-performance liquid chromatography. SETTING: Research laboratory. PATIENT(S): Two hundred sixty-eight men seeking infertility counseling and 254 partners of infertile women. INTERVENTION(S): We studied three MTHFR (c.1286A → C, c.665C → T and c.203G → A) and two MTRR (c.66A → G and c.524C → T) single-nucleotide polymorphisms and characterized sperm parameters in both oligozoospermic and normospermic men. A cohort of 522 men was examined for this study. A subgroup of 103 men was constituted for quantification of Hcy levels. MAIN OUTCOME MEASURE(S): Semen samples were collected for determinations of sperm concentration, motility, and morphology according to World Health Organization guidelines as well as for DNA isolation. Blood samples of the corresponding individuals were obtained to quantify plasma homocysteine levels. RESULT(S): We did not observe a relationship between homocysteinemia and sperm counts. The MTHFR c.665C → T variant is associated with mild hyperhomocysteinemia in blood plasma in the TT homozygous state. CONCLUSION(S): No association was found between MTHFR/MTRR genetic variants and sperm counts. Although no association was observed with reduced sperm counts, the MTHFR 665TT genotype is associated with a significant increase in blood plasma homocysteine levels.

Learning curve of transvaginal ultrasound for the diagnosis of endometriomas assessed by the cumulative summation test (LC-CUSUM).

A specific statistical tool (the cumulative summation test for learning curve or LC-CUSUM) was used to monitor the learning curve of four trainees for the diagnosis of endometriomas by transvaginal ultrasound. A large intertrainee variability in the learning curves was found, justifying a tailored training to learn this diagnosis.

Smoking among French infertility specialists: habits, opinions and patients' management.

OBJECTIVE: The deleterious effects of tobacco on fertility are now largely demonstrated. Little is known, however, about how infertility doctors communicate on smoking and about their own smoking habits. In this study, we examined smoking habits among French infertility specialists and their attitudes towards infertile couples' exposure to tobacco. STUDY DESIGN: A postal survey was sent in 2009 to the 803 French certified physicians (gynaecologists, urologists, endocrinologists and embryologists) specializing in infertility. Demographical data, smoking habits and attitude towards patients' smoking were recorded. Statistical analysis and multiple correspondence analysis were performed in order to identify differences among physicians according to age, gender, occupation or smoking status. RESULTS: Response rate was 42.3%. Half of the respondents were male, 41% were under 45 years, 37% were embryologists and 53.3% were gynaecologists. Thirteen percent reported current smoking. More than 80% always asked their patients about smoking status and cannabis consumption. Most physicians specifically informed infertile couples on tobacco, advised them to quit and proposed smoking cessation therapies. Only 24% refused care unless smoking cessation occurred. Statistical analysis showed some differences among subgroups according to gender, occupation or age. Surprisingly, results were comparable according to smoking status. CONCLUSION: Most infertility specialists are aware of the deleterious effects of tobacco on fertility and ask their patients to quit. The heterogeneity in infertile patients' management, however, underlines the need for better professional and patients' information on smoking.

Monozygotic triplet pregnancies after single blastocyst transfer: two cases and literature review.

Following IVF, single blastocyst transfer has been thought to reduce the risks of high-order multiple pregnancies. This is a report of two cases of monozygotic triplet pregnancies after single blastocyst transfer and a review of the current concepts of the pathogenesis of multiple monozygotic pregnancies as well as the options for managing these high-risk pregnancies. Both cases were reduced to a twin pregnancy by selective cord coagulation at 15-16 weeks. Whereas one patient had uneventful pregnancy until labour was induced for growth arrest and cord Doppler abnormalities in one twin, the other developed a severe twin-to-twin transfusion syndrome which required fetoscopic laser surgery at 21 weeks. In both cases, healthy twins were delivered by Caesarean section at 34.5 and 34 weeks, respectively. As the predictors of their occurrence are not fully understood, patients should be informed of the risks of monozygotic pregnancies after single blastocyst transfer.

Results of first in vitro fertilization cycle in women with colorectal endometriosis compared with those with tubal or male factor infertility.

This retrospective study of women undergoing IVF (29 with colorectal endometriosis, 157 with tubal factor infertility, and 340 with male factor infertility) found similar fertility outcomes between the groups.

Predictive value of ovarian reserve markers in smoking and non-smoking women undergoing IVF.

Ovarian reserve markers are now widely used in IVF centres in order to predict ovarian response and adapt ovarian stimulation protocols. In this study, the respective performance of day-3 FSH, oestradiol and anti-Müllerian hormone concentrations and antral follicle count for the prediction of poor ovarian response to ovarian stimulation and pregnancy in IVF cycles were compared in women according to their smoking status. The analysis of 384 IVF cycles showed that anti-Müllerian hormone concentration and antral follicle count were the best predictors of poor ovarian response and performed better in non-smokers than in smokers, for which no parameter could predict pregnancy.

How soon can I be proficient in embryo transfer? Lessons from the cumulative summation test for learning curve (LC-CUSUM).

BACKGROUND: Embryo transfer, a crucial step for achieving pregnancy after in vitro fertilization, is an operator-dependent technique but the number of procedures required for a trainee to reach proficiency is unknown. We set out to evaluate the learning curve (LC) of embryo transfer using a specifically designed statistical tool. METHODS: The first embryo transfers performed by five trainees were monitored by the cumulative summation test for learning curve (LC-CUSUM), a statistical tool designed to indicate when a process has reached a predefined level of performance. The main outcome measure was a positive hCG test. A 40% pregnancy rate (PR) per transfer was chosen to define adequate performance and a PR of 20% was considered inadequate. After the learning phase, standard CUSUM were implemented to ensure that performance was maintained. The same CUSUM parameters were also applied to monitor 241 consecutive embryo transfers performed by a senior gynaecologist. RESULTS: Between 11 and 99 embryo transfers were necessary for the trainees to reach the predefined level of performance. Simple and intuitive graphical representations of the LCs were generated. CUSUM tests confirmed that performance was maintained after the learning phase. The PR of the senior gynaecologist was 42.7% and the CUSUM showed that performance remained adequate throughout the 241 procedures. CONCLUSIONS: This study provides an exportable model for a quantitative monitoring of the LC of embryo transfer as well as a reference curve for continuous monitoring of performance in embryo transfer. The length of the LC of embryo transfer is highly variable, justifying a tailored training to learn this procedure.

Arterial cord blood lactate at birth correlates with duration of pushing efforts.

OBJECTIVE: To evaluate the impact of the duration of pushing efforts on arterial cord blood lactate values. METHODS: This was a prospective observational study of 124 consecutive normal vaginal deliveries in a tertiary teaching hospital. Arterial cord blood lactate was determined immediately at birth with a test strip method. Univariate and multivariate analyses were performed to check for clinical determinants of lactate levels. The main measure was lactate according to the duration of pushing efforts. RESULTS: Arterial cord lactates increased significantly and were strongly correlated with the duration of pushing efforts, independent of gestational age and birthweight. Women pushing for more than 20 min had higher arterial cord blood lactates (4.9 +/- 1.4 vs. 3.3 +/- 1.16 mM, respectively) and a higher rate of lactates >6 mM (18 vs. 3%) than those pushing for less than 20 min. CONCLUSION: At normal delivery, arterial cord blood lactates increase significantly with the duration of pushing efforts. Pushing for more than 20 min is associated with an increased risk of metabolic acidosis in the neonate. Further studies are required to evaluate the clinical significance of these observations.