Study of postoperative complications after the implementation of a multidisciplinary care pathway for patients with digestive endometriosis.

PURPOSE: To assess the quality of care following the establishment of a multidisciplinary care pathway for patient operated on for deep pelvic endometriosis with digestive impairment. METHODS: We conducted a retrospective monocentric study of patients suffering from deep infiltrating endometriosis, treated in Gynaecological Department at Toulouse University Hospital from January 2018 to December 2020. We compared our results to those of our previous study, Gornes et al. which showed a postoperative complication occurred in 37.8% of the cases and a postoperative severe complication according to the Clavien-Dindo classification (grades 3b) rate of 18.3%. RESULTS: 98 patients were included. Our study shows a clear decrease in postoperative complications with an overall complication rate of 19.4% and severe complications (grades 3b) of 4.1%. The rate of complication appeared to be significantly less frequent in the case of shaving in relation to other digestive procedures (p = 0.008) and in the case of a lesion of < 20 mm by MRI (p = 0.01). The use of multidisciplinary surgical care was more frequent in the case of multiple locations (66.7% vs. 41.8%, p = 0.07) and was more frequent in the case of transmural damage with echo endoscopy (and to a lesser degree in the case of damage of the muscularis or mucous membrane) (p = 0.05). CONCLUSIONS: Multidisciplinary care of endometriosis with digestive damage appears to be indispensable. The intraoperative intervention of a skilled digestive surgeon of bowel endometriosis helps create the best balance between effectiveness-complications-functional prognosis, with a reduction of severe postoperative complications.

Is in vitro maturation of oocytes retrieved ex vivo from ovarian tissue an effective fertility preservation technique in the presence of organic ovarian cysts?

OBJECTIVE(S): In vitro maturation (IVM) of oocytes retrieved ex vivo from ovarian tissue (OTO-IVM) could be an additional source of mature oocytes with the potential to optimise medical fertility preservation (FP) after oophorectomy. It is often undertaken at the same time as the ovarian tissue cryopreservation (OTC). In the presence of an organic ovarian cyst, OTO-IVM could prove to be the only technique available to permit FP since ovarian stimulation, transvaginal ovarian needle puncture or future ovarian tissue graft are contraindicated. However, the presence of an organic cyst could alter follicular growth and the number of retrievd oocytes. Our study aims to assess the efficiency of OTO-IVM in such situations. STUDY DESIGN: Retrospective, observational study involving 20 female patients with FP by OTO-IVM between May 2017 and November 2021 at the University Hospital of Toulouse. Oocytes retrieved "ex vivo" were transferred to an IVM medium with HP-hMG, LH and HSA and then vitrified after 24 to 48 h of IVM. Data analysis was performed on the total population and comparatively between patients who had or did not have an organic ovarian cyst. RESULTS: The indications included 15 oncologic and 5 non-oncologic indications. Ten had an organic ovarian cyst on the retrieved ovary. The number of retrieved oocytes was 17.4+/-12.0 in the absence of cyst vs 4.1+/-6.3 in the presence (p = 0.003). The number of vitrified mature oocytes was 5.8+/-5.3 in the absence vs 1.1+/-2.2 (median = 0) in the presence of a cyst (p = 0.03). Ninety percent of the patients with an organic cyst had less than two vitrified mature oocytes. The mean maturation rate was 34%, not significantly different between the two groups. We found a correlation between serum AMH level and the number of mature oocytes: ρ:0.47 CI95 = [0.02; 0.76]; p = 0.04. CONCLUSION(S): OTO-IVM is an additional source of mature oocytes to optimise FP after oophorectomy. However, in the presence of an organic ovarian cyst on the retrieved ovary, the exocrine, paracrine and endocrine functions of the ovary are impaired. As such, the number of immature oocytes obtained is highly impacted and appears to be insufficient to be able to propose systematically this technique in such situations.

Spontaneous pregnancy rate following surgery for deep infiltrating endometriosis in infertile women: The impact of the learning curve.

OBJECTIVES: To determine whether the surgical learning curve impact the spontaneous pregnancy rate in infertile patients undergoing removal of deep infiltrating endometriosis MATERIAL AND METHODS: Single center retrospective study including the first 50 consecutive infertile women suffering from deep infiltrating endometriosis and referred to a single surgeon. All patients underwent laparoscopic removal of deep endometriosis lesions. The study population was stratified in two subgroups, namely the early group (including the first 25 cases) and the late group (comprising the 25 subsequent cases). Pregnancy and live birth rates, surgical morbidity and clinical recurrence rate were compared between study groups. RESULTS: Overall, spontaneous pregnancy rate (40 % in the early group versus 56 % in the late group, p = 0.25), live birth rate (40 % versus 44 %, p = 0.77) and clinical recurrence rate (16 % versus 4%, p = 0.16) did not significantly differ between the study groups. Logistic regression analysis revealed that ASRM stage, EFI score, and body mass index were the only significant prognostic factors of postoperative spontaneous fertility. CONCLUSION: Surgical resection of deep infiltrating endometriosis in infertile women is associated with high spontaneous pregnancy and live birth rates. The surgeon's learning curve does not impact postoperative fertility outcomes.

Potential chances for natural fertility influence results of intrauterine inseminations.

OBJECTIVE: Intra-uterine insemination (IUI) is widely used for different indications. The aim of the present study was to evaluate the efficiency of intra-uterine insemination as a function of indication and origin of the inseminated spermatozoa. STUDY DESIGN: The retrospective study involved 827 first attempts of IUI in 827 couples between January 2011 and July 2017 in the Toulouse university hospital. Of these, 642 used fresh sperm from the husband, 40 frozen sperm from the husband and 145 frozen sperm from donors. The measured outcome parameter was live birth rate per attempt. RESULTS: When comparing couples lacking functional gametes (due to male or female causes), to couples who could potentially conceive spontaneously, i.e. subfertile, the latter were found to have a significantly lower live birth rate (18% vs 26%; P < 0.05). Even when adjusted for demographic parameters, which differed significantly between the 2 groups (female age, percentage of women suffering from primary infertility, BMI, number of inseminated motile spermatozoa and stimulation duration), this difference remained statistically significant (OR = 0.639 [0.425-0.961]; P = 0.0316). CONCLUSION: When compared to couples lacking functional gametes, subfertile couples have poor IUI outcomes, suggesting a hidden cause of infertility, despite no apparent differences in ovarian reserve, tubal potency, results of ovarian stimulation and normal conventional sperm parameters. Further studies are required to better characterise and identify this subgroup of women with poor IUI outcomes.

Age-specific anti-Mullerian hormone (AMH) levels poorly affects cumulative live birth rate after intra-uterine insemination.

OBJECTIVE: To evaluate the impact of age-specific anti-Mullerian (AMH) levels on the cumulative live birth rate after 4 intra uterine inseminations (IUI). STUDY DESIGN: The retrospective study study involved 509 couples who underwent their first IUI between January 2011 and July 2017 in the Toulouse University Hospital. All IUI were performed after an ovarian stimulation combining recombinant FSH and GnRH antagonist. The main measure outcome was the cumulative live birth rate (LBR) defined as the number of deliveries with at least one live birth resulting from a maximum of 4 IUI attempts. RESULTS: When compared to normal or high levels, low age-specific AMH (<25th of the AMH in each age group) was associated to a non-significant lower live birth rate (31%, 38% and 42% respectively for low, normal and high age-specific groups; P = 0.170) and non-significant higher miscarriage rate (26%; 19% and 14% respectively for low, normal and high age-specific groups; P = 0.209). However, it must be pointed out that in low age-specific AMH the initial FSH doses used for stimulation were higher than in the other groups. CONCLUSION: This study shows that the age-specific levels of AMH have only a slight effect on IUI outcome when adapting the stimulation protocols to their level.

Association between progesterone to number of mature oocytes index and live birth in GnRH antagonist protocols.

RESEARCH QUESTION: What is the association between blood progesterone level alone, progesterone to mature oocytes index (PMOI) and IVF outcomes? DESIGN: Clinical data from 960 couples undergoing their first fresh embryo transfer after an intracytoplasmic sperm injection attempt carried out between September 2012 and July 2017 were analysed. All patients underwent ovarian stimulation combining recombinant FSH and gonadotrophin releasing hormone antagonist. Progesterone was measured on the day on which ovulation was triggered. The PMOI was divided into four groups based on 25th, 50th and 75th percentiles, and live birth and implantation rates were compared between the groups. RESULTS: A negative association was found between PMOI levels, live birth and implantation rates. When adjusting for age, ovarian stimulation index (OSI) and number of embryos transferred, the PMOI remained negatively correlated to live birth rate (LBR) (OR = 0.147 [0.031 to 0.701]; P = 0.0161), whereas total blood progesterone was no longer evident. Moreover, the LBR (18.5% versus 28.4%; P < 0.01) and implantation rate (12.4% versus 21.0%; P < 0.01) were significantly decreased only when PMOI was 0.167 ng/ml or greater, irrespective of progesterone concentration (< or ≥1.08 ng/ml). The opposite was not true, however. Similar PMOIs were recorded in the same patient from one attempt to the next, and were partially linked to basal FSH, anti-Müllerian hormone, antral follicle count and OSI. CONCLUSIONS: PMOI seems to be more predictive than total progesterone level of IVF outcome and reflects the ability of embryos to develop as it is linked to the implantation rate.

Establishment and validation of a score to predict ovarian response to stimulation in IVF.

This study aimed to integrate clinical and biological parameters in a score able to predict ovarian response to stimulation for IVF in gonadotrophin-releasing hormone (GnRH) antagonist protocols. A progressive discriminant analysis to establish a score including the main clinical and biological parameters predicting ovarian response was performed by retrospectively analysing data from the first ovarian stimulation cycle of 494 patients. The score was validated in a prospectively enrolled, independent set of 257 patients undergoing their first ovarian stimulation cycle. All ovarian stimulations were performed using a combination of GnRH antagonist and recombinant FSH. Ovarian response was assessed through ovarian sensitivity index (OSI). Parameters from the patients' database were classified according to correlation with OSI: the progressive discriminant analysis resulted in the following calculation: score = 0.192 - (0.004 × FSH (IU/l)) + (0.012 × LH:FSH ratio) + (0.002 × AMH (ng/ml)) - (0.002 × BMI (kg/m2)) + (0.001 × AFC) - (0.002 × age (years)). This score was significantly correlated with OSI in the retrospective (r = 0.599; P < 0.0001) and prospective (r = 0.584; P < 0.0001) studies. In conclusion, the score including clinical and biological parameters could explain 60% of the variance in ovarian response to stimulation.

Effect of unilateral tubal abnormalities on the results of intrauterine inseminations.

A total of 101 patients with one normal tube were compared with 117 patients with two normal tubes to assess the effect of unilateral tubal abnormalities on the results of intrauterine inseminations. The clinical pregnancy and live birth rates seemed to reduce by one-half in almost all types of abnormality, suggesting that these patients should be preferentially treated with IVF.

How many embryos should be transferred? A validated score to predict ongoing implantation rate.

OBJECTIVE: To developed a prognostic score to predict ongoing implantation rate according to clinical and biological parameters and to choose the number of embryos to be transferred in patients undergoing IVF/ICSI. STUDY DESIGN: The transfer score was established using multivariate analysis of biological and clinical parameters in 3211 fresh embryo transfers in a retrospective study. Then we validated the score in 694 fresh embryo transfers in a prospective study. We assessed ongoing implantation rates, ongoing pregnancy rates, multiple pregnancy rates and live birth rate. RESULTS: Among the different variables tested, 4 were identified that influenced the implantation rate: female age, the ratio of retrieved oocytes/mean daily dose of injected FSH, attempt rank and the morphology of the embryo cohort. Prospective application of this score resulted in significantly lower number of transferred embryos (1.8 vs 2.0 P<0.001) and lower twins rates (9.7% vs 17.3%, P<0.001) without decreasing live birth rates. CONCLUSION: Although the risks of multiple pregnancies should not be ignored, it appears excessive to impose the limit of 2 embryos for transfer particularly in situations with a poor prognosis. We sought to provide a personalized prognosis by using clinical and embryo data in order to choose the number of embryo(s) for transfer with a moderate multiple pregnancy rate of less than 11%.

Parenthood and separation in couples 6 years after their first infertility consultation.

OBJECTIVE: To evaluate the percentage of couples achieving parenthood and the rate of separation 6 years after their first consultation for infertility. STUDY DESIGN: Epidemiological study in the reproductive medicine department of a French university hospital. All first consulting couples (FCC) who had their first infertility consultation in the department in 2007 were contacted by phone and asked to respond to a questionnaire concerning their infertility treatments, parenthood and marital status 6 years after their first consultation. RESULTS: Of the 685 FCC, 94 could not be contacted, 34 refused to respond and 557 (86%) answered the questionnaire. Of 557 FCC who have responded, 361 (65%) have achieved parenthood: 166 (46%) after treatment, 98 (27%) after spontaneous conception, 38 (11%) after both spontaneous and treatment-induced conception and 59 (16%) through adoption. Parenthood was not influenced either by the causes or duration of infertility. Separation occurred in 53 (9.5%) of FCC, mainly in those without any children (28% vs 4% in FCC with at least one child; P<.0001). CONCLUSION: Six years after their primary consultation, 25% of couples remained childless and 28% of them were separated.

Clinical and biological parameters influencing implantation: score to determine number of embryos to transfer.

Choosing the number of embryos to be transferred is a major problem in assisted reproductive technologies. This study aimed to establish and validate a score predicting implantation rates in order to help in the choice of the number of embryos to be transferred, allowing the best compromise between high pregnancy rate and low multiple pregnancy risk. Clinical and biological parameters influencing implantation rates were retrospectively analysed in 739 embryo transfers and an implantation score was established. This score was then prospectively validated in 521 embryo transfers. Three parameters (age, ovarian response to FSH stimulation and embryo morphology) appeared to be predictive of the implantation rates and were included in an implantation score (3-9). The prospective study confirmed the validity of the score since implantation rates were higher when the score increased (5.9% for score 3 versus 22.4% for score 9; P < 0.05). Therefore, success rates can be predicted by the implantation score, which is of clinical value in choosing the number of embryos to be transferred in order to decrease multiple pregnancies while keeping high pregnancy rates. However, choosing the right number of embryos to be transferred needs further studies, since the percentage of multiple pregnancies remained relatively high in this prospective study (27%).

Rupture of a uterine horn after laparoscopic salpingectomy. A case report.

BACKGROUND: Uterine rupture after salpingectomy, especially associated with cornual resection, is a rare, serious pregnancy complication. CASE: A spontaneous uterine rupture occurred during the second trimester of pregnancy, following salpingectomy with resection of the interstitial portion. Conservative treatment was performed, and fertility was preserved. CONCLUSION: Postsalpingectomy pregnancies must be carefully and frequently monitored, with ultrasonography used at the slightest clinical symptom. A postsalpingectomy rupture must be treated surgically, preferably with conservative treatment rather than hysterectomy.

A computerized decision support system for ovarian stimulation by gonadotropins.

OBJECTIVE: To evaluate the effectiveness of a computerized decision support system for ovarian stimulation with gonadotropins. DESIGN: Retrospective and prospective randomized studies. SETTING: Private and university teaching hospital. PATIENT(S): Women undergoing ovarian stimulation to treat infertility. MAIN OUTCOME MEASURE(S): Pregnancy rate. RESULT(S): In the retrospective study, computer-generated decisions were compared with clinicians' decisions in 118 stimulated cycles in 53 patients. In 90% of cases, the choice of FSH regimens and adjustments to dosages were identical. In the prospective study, the computer-generated decisions achieved a pregnancy rate per cycle of 18% (15 of 82 cycles), compared with 16% (13 of 82 cycles) achieved by clinicians. CONCLUSION(S): A computerized decision making system was as effective as skilled clinicians in achieving pregnancy by using ovarian stimulation with FSH.

Reaçäo acrossômica na exploraçäo de infertilidade masculina em fecundaçäo in vitro / Place of acrosomal reaction in the exploration of male infertility in in vitro fertilization

O acrossoma, vesícula de origem golgiana, tem um papel essencial no desenvolvimento da fecundaçäo, tanto in vivo com in vitro. Neste artigo estudaram diferentes métodos de induçäo da reaçäo cromossômica (RA). Os indutores como o líquido folicular, a progesterona e o cálcio iônico permitem a exploraçäo da dinâmica da RA e a análise dos espermatozóides aptos a realizar esta RA. Este trabalho mostra o interesse destas exploraçöes nos casos de infertilidade masculina em Reproduçäo Assistida.