Lionel Dessolle

Determinants of pregnancy rate and obstetric outcome after laparoscopic myomectomy for infertility

Abstract Objective: To determine the effect of myomectomy on infertility and to assess the factors influencing reproductive outcome. Design: Retrospective study. Setting: Tertiary care center. Patient(s): One hundred and three infertile women with uterine leiomyoma who had had infertility >2 years and a follow-up time >12 months were enrolled. Follow-up was complete for 88 patients, including 28 (31.8%) with primary infertility and 44 (50%) with unexplained infertility. The mean (±SD) age of the patients was 36.1 ± 2.1 years. Intervention(s): Laparoscopic myomectomy. Main Outcome Measure(s): Pregnancy rate according to patient and fibroid characteristics. Result(s): Forty-two patients became pregnant (40.7%). The mean (±SD) delay in conception was 7.5 ± 2.6 months. Nearly 80% of the women conceived spontaneously. Of 44 pregnancies in 42 women, 36 live newborns were delivered. No dehiscence of uterine scar occurred. The pregnancy rate was significantly higher in women P Conclusion(s): Fertility and pregnancy after laparoscopic myomectomy depend primarily on patient age, duration of infertility before myomectomy, and existence of associated infertility factors.

Determinants of pregnancy rate in the donor oocyte model: a multivariate analysis of 450 frozen-thawed embryo transfers

BACKGROUND Conflicting results have been published about the determinants of pregnancy after oocyte donation (OD). We used the OD model to determine predictive factors of pregnancy in the recipient after frozen-thawed embryo transfer (FTET) in a specific series where all the embryos were cryopreserved without any prior selection for fresh transfer. METHODS We report a retrospective study in a university tertiary care center. Multivariate analysis and logistic regression were used to identify predictive factors of pregnancy in a series of 450 OD FTET cycles in 198 infertile women between January 1992 and December 2006. RESULTS The mean (+/-SD) recipient age was 35.7 (+/-4.5). Impaired ovarian function was the main indication for OD. The mean +/- SD (range) number of embryos transferred was 1.65 +/- 0.5 (1-3). Overall clinical pregnancy, implantation and delivery rates were 30, 18 and 23%, respectively. After univariate analysis, pregnancy rates were significantly higher in recipients under 35 years, in women with a body mass index (BMI) <30 kg/m(2), in women with an endometrial thickness of > or =8 mm, in amenorrheic women and in women not receiving pituitary down-regulation before endometrial preparation. Using multivariate analysis, the BMI, endometrial thickness and the use of pituitary down-regulation were independent predictors of pregnancy, regardless of age. CONCLUSIONS This study supports that endometrial thickness of <8 mm, obesity and the use of GnRH analogue pituitary down-regulation before endometrial priming negatively impact pregnancy rates, independently of the recipients age.

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

PurposeSmoking 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.MethodsAFC, 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.ResultsActive 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.ConclusionActive 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.

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.

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.

Results of recto-vaginal fistula repair: retrospective analysis of 48 cases

OBJECTIVE To evaluate the long-term outcome of the Musset technique of recto-vaginal fistula (RVF) repair. STUDY DESIGN During the years 1992-1998, 48 women underwent recto-vaginal fistula repair. A retrospective study in a university tertiary referral center was conducted. RESULTS The main etiologies were obstetrical trauma (25), local infection (11), inflammatory disease (7), and post surgery (3). Thirty women (63%) had a previous fistula repair failure. The mean+/-S.D. fistula diameter was 1.4+/-1.0, and in 40% of the patients the fistula diameter was >2.5cm. In 19 cases (39.6%) there was a complete opening of the perineum and anal sphincter. Gas and stool incontinence before the operation were noted in 85 and 75% of the patients, respectively. Successful anatomic results were achieved in all patients. Five patients were re-operated due to gas and stool incontinence, and all but one had satisfactory anatomic and functional satisfactory results. The success rates in women with Crohns disease and with a previous RVF repair failure were 100 and 98%, respectively. No major intra or postoperative complications were noted. CONCLUSION The Musset procedure provide excellent anatomic and functional results and women with Crohns disease or previous RVF repair have comparable long-term results.

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.

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). METHODS 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.

A cycle-based model to predict blastocyst transfer cancellation

BACKGROUND Extended culture for blastocyst transfer is thought to result in embryos with high implantation potential, enabling the transfer of fewer embryos and the reduction of multiple pregnancies after in vitro fertilization (IVF). However, one major drawback of extended culture is the risk of transfer cancellation if no blastocyst develops by Day 5, despite the observation of adequate early embryo development. We set out to develop a model to predict blastocyst transfer cancellation. METHODS The model was built from 562 consecutive first IVF cycles and tested on an independent validation cohort. Multivariable logistic regression analysis was used to test the association of patient and cycle characteristics with the presence of cultured blastocysts on Day 5 and to create a nomogram. The models performance was quantified by discrimination and calibration and clinical utility was evaluated for various thresholds. RESULTS Fertilization technique, number and quality ratio of the Day 3 embryos and female age were independently associated with blastocyst development. The final prediction model showed an area under the curve (AUC) of 0.75 in the training set (95% confidence interval (CI): 0.73-0.77) and was well calibrated. The AUC for the validation data set was 0.80 (95% CI: 0.78-0.83) and calibration was acceptable. Using a decision threshold of 0.55, the model showed a negative predictive value of 80.5% and a false positive rate of 17%. CONCLUSION A cycle-based model could prove clinically-relevant for reducing the incidence of cancelled Day 5 transfers.

Learning curve of vitrification assessed by cumulative summation test for learning curve (LC-CUSUM)

We used the cumulative summation test for learning curve (LC-CUSUM), a specifically designed statistical tool, to evaluate the first 50 procedures performed by a trainee in vitrification and to provide a usable model for monitoring the learning process of this technique. Given the lack of models to evaluate IVF technologies, the CUSUM methodology could prove useful for quality control in laboratories.