[French clinical practice guidelines developed by a modified Delphi consensus process for oocyte vitrification in women with benign gynecologic disease]. / Indications de vitrification ovocytaire dans les pathologies gynécologiques bénignes : conseils de bonne pratique du CNGOF après étude de consensus par méthode Delphi.

OBJECTIVES: To provide clinical practice guidelines about fertility preservation (FP) for women with benign gynecologic disease (BGD) developed by a modified Delphi consensus process for oocyte vitrification in women with benign gynecologic disease. METHODS: A steering committee composed of 14 healthcare professionals and a patient representative with lived experience of endometriosis identified 42 potential practices related to FP for BGD. Then 114 key stakeholders including various healthcare professionals (n=108) and patient representatives (n=6) were asked to participate in a modified Delphi process via two online survey rounds from February to September 2020 and a final meeting. Due to the COVID-19 pandemic, this final meeting to reach consensus was held as a videoconference in November 2020. RESULTS: Survey response of stakeholders was 75 % (86/114) for round 1 and 87 % (75/86) for round 2. Consensus was reached for the recommendations for 28 items, that have been distributed into five general categories: (i) Information to provide to women of reproductive age with a BGD, (ii) Technical aspects of FP for BGD, (iii) Indications for FP in endometriosis, (iv) Indications for FP for non-endometriosis BGD, (v) Indications for FP after a fortuitous diagnosis of an idiopathic diminished ovarian reserve. CONCLUSION: These guidelines provide some practice advice to help health professionals better inform women about the possibilities of cryopreserving their oocytes prior to the management of a BGD that may affect their ovarian reserve and fertility. STUDY FUNDING/COMPETING INTEREST(S): The CNGOF (Collège National des Gynécologues Obstétriciens Français) funded the implementation of the Delphi process.

Gynaecological endoscopic evaluation of 4% icodextrin solution: a European, multicentre, double-blind, randomized study of the efficacy and safety in the reduction of de novo adhesions after laparoscopic gynaecological surgery.

BACKGROUND: Gynaecological laparoscopic surgery outcomes can be compromised by the formation of de novo adhesions. This randomized, double-blind study was designed to assess the efficacy and safety of 4% icodextrin solution (Adept(®)) in the reduction of de novo adhesion incidence compared to lactated Ringer's solution (LRS). METHODS: Patients undergoing laparoscopic surgery for removal of myomas or endometriotic cysts were treated with randomized solution as an intra-operative irrigant and 1l post-operative instillate. De novo adhesion incidence (number of sites with adhesions), severity and extent were independently scored at a second-look procedure and the efficacy of the two solutions compared. The effect of surgical covariates on adhesion formation was also investigated. Initial exploratory analysis of individual anatomical sites of clinical importance was progressed. RESULTS Of 498 patients randomized, 330 were evaluable (160 LRS--75% myomectomy/25% endometriotic cysts; 170 Adept--79% myomectomy/21% endometriotic cysts). At study completion, 76.2% LRS and 77.6% Adept had ≥ 1 de novo adhesion. The mean (SD) number of de novo adhesions was 2.58 (2.11) for Adept and 2.58 (2.38) for LRS. The treatment effect difference was not significant (P = 0.909). Assessment of surgical covariates identified significant influences on the mean number of de novo adhesions regardless of treatment, including surgery duration (P = 0.048), blood loss in myomectomy patients (P = 0.019), length of uterine incision in myomectomy patients (P < 0.001) and number of suture knots (P < 0.001). There were 15 adverse events considered treatment-related in the LRS patients (7.2%) and 18 in the Adept group (8.3%). Of 17 reported serious adverse events (9 LRS; 8 Adept) none were considered treatment-related. CONCLUSIONS: The study confirmed the safety of Adept in laparoscopic surgery. The proportion of patients with de novo adhesion formation was considerably higher than previous literature suggested. Overall there was no evidence of a clinical effect but various surgical covariates including surgery duration, blood loss, number and size of incisions, suturing and number of knots were found to influence de novo adhesion formation. The study provides direction for future research into adhesion reduction strategies in site specific surgery.

Does prevention of intraperitoneal spillage when removing a dermoid cyst prevent granulomatous peritonitis?

In this retrospective study of 314 patients undergoing surgery for ovarian dermoid cysts, conducted over a 20-year period, we evaluated the impact of the routine use of laparoscopic surgery without recourse to laparotomy to retrieve the specimen, using an endoscopic retrieval bag placed under the cyst to prevent intraperitoneal spillage of cyst contents, and subsequent postoperative granulomatous peritonitis. Accidental cyst rupture was more frequent when a total laparoscopic approach was used (26/174 or 15% versus 39/140 or 28%; P = 0.005), but there were no cases of intraperitoneal spillage when an endoscopic bag was used. Two cases of granulomatous peritonitis developed out of 26 women with intraperitoneal spillage of cyst contents (8%). We conclude that the risk of granulomatous peritonitis can be minimised by undertaking laparoscopic removal of dermoid cysts with the routine intraoperative use of an endoscopic retrieval bag to prevent intraperitoneal spillage of cyst contents.

Ovarian epithelial dysplasia after ovulation induction: time and dose effects.

BACKGROUND: Ovarian epithelial dysplasia was first described after prophylactic oophorectomies for genetic risk. Ovarian stimulation has been considered as a risk factor of ovarian cancer by Fathalla's incessant ovulation theory. In this study, we have investigated the risk of ovarian dysplasia after ovulation induction. METHODS: We reviewed 99 oophorectomies or cystectomies between 1990 and 2005 divided them into two groups: previous in vitro fertilization (n = 37) and a panel of fertile controls (n = 62). Eleven epithelial cytological and architectural features were defined and an ovarian epithelial dysplasia score was calculated to quantify the degree of ovarian epithelial abnormalities. RESULTS: All the ovaries were macroscopically non-cancerous except in two patients (one endometrioid cancer and one borderline tumour). The mean ovarian dysplasia score was significantly higher in the ovulation induction group than in the control group (7.64 versus 3.62, P = 0.0002). We also found a relationship between the number of ovulation-inducted cycles and the severity of ovarian dysplasia ('dose-effect') and a relationship between time after the end of ovulation induction (over 7 years) and the severity of ovarian dysplasia ('time-effect'). CONCLUSIONS: There is probably a relationship between ovarian epithelial dysplasia and either ovulation inducing drugs or infertility. By Fathalla's incessant ovulation theory, 'the dose effect and the time effect' of ovarian stimulation may explain ovarian dysplasia formation.

[Ovarian stimulation for IVF in France: choice and results according to protocols and gonadotrophin]. / La stimulation de l'ovulation pour fécondation in vitro, en France : choix et résultats en fonction des protocoles et des gonadotrophines.

OBJECTIVE: The study objective was to analyze the ovarian stimulation practice in Assisted Reproductive Technology (ART) in France, to determine the factors influencing this practice and to analyze its impact on ART results. MATERIALS AND METHODS: The study included all the cycles forms transmitted by the centres to the Agence de la biomédicine on FIVNAT forms and then transmitted from the agency to FIVNAT. All cycles with missing data or inconsistencies on ovarian stimulation and spontaneous cycles were excluded, leaving 18,601 cycles for analysis. The protocols were classified in four groups: agonists with short protocol, with long protocol, antagonists and cycles without GnRH agonists. Gonadotropins were regrouped in four groups: recombinant FSH, urinary FSH, HMG, and association of FSH (urinary or recombinant) and HMG. RESULTS: If the basal protocol usually combines GnRH agonists with long protocol and recombinant FSH, the study shows that some patients characteristics, particularly women's age, ovulation status and previous failures have a large influence on other choices for protocol (short protocol, antagonists) and gonadotropins. Concerning the impact on ART outcome, if short protocols remain associated to the worse results, there was little difference between long protocol and antagonists and according to the gonadotropin choice. DISCUSSION AND CONCLUSION: This study allows to know better on ovarian stimulation practice in ART in France.

Estimating the success of an in vitro fertilization programme using multiple imputation.

BACKGROUND: The outcome of in vitro fertilization (IVF) has been widely investigated over the last 30 years, but evaluation was mostly based on pregnancy rate per oocyte retrieval. Our objective was to estimate the cumulative live birth rate after four IVF aspirations, using multiple imputation that takes into account treatment interruptions. METHODS: We analysed data from 3037 couples beginning IVF treatment between 1998 and 2002 in two French IVF units. Multiple imputations were used at each aspiration to impute the IVF outcome (delivery or not) for couples who interrupted treatment. The global success rate after four aspirations was then computed. RESULTS: At the first aspiration, 21% of couples obtained a live birth and 24% discontinued treatment. The multiple imputation method provided an estimated cumulative live birth rate at each aspiration as if no couple discontinued treatment: 35% at the second aspiration and 41% at the third. The cumulative success rate after four aspirations was estimated at 46% (95% CI: 44-48%). CONCLUSIONS: Multiple imputation is a promising method for estimating the cumulative success rate of IVF. It could provide new insight on IVF evaluation and should be tested in further studies.

[Ovarian epithelial dysplasia: myth or reality? Review]. / Dysplasie épithéliale ovarienne: mythe ou réalité? Revue de la littérature.

Ovarian epithelial dysplasia has been described in the ovarian surface epithelium by histologic, morphometric and nuclear profile studies. It could represent a potential precursor of ovarian malignancy in patients with genetic risk of ovarian cancer, although its natural history and progression to carcinoma are unpredictable. Diagnosis and identification of ovarian dysplasia would certainly be useful to understand the early steps of ovarian carcinogenesis. However, dysplasia in relation with ovulation induction seems to have a different pattern. We report dysplasia definitions and the current clinical management.

[Are there anatomical and clinical correlations between minimal and deep endometriosis? First results of Auvergne's Registry of Endometriosis]. / Existe-t-il une corrélation anatomoclinique entre endométriose minime et endométriose sévère? Premiers résultats du registre régional d'Auvergne de l'endométriose.

OBJECTIVE: With a prospective study, to evaluate the existence of two distinct clinical diseases in the endometriosis syndrome, by comparing pain symptoms and quality of life from patients with minimal endometriosis (AFS-R<5) and data from patients with severe disease (deep infiltrating nodules and/or ovarian endometrioma). PATIENTS AND METHODS: Patients with minimal disease (group A with AFS-R<5) and severe endometriosis (group B) are selected from the Auvergne Endometriosis Registry which started in January 2004. They have never been treated before for endometriosis. A surgical laparoscopic and a pathological diagnosis are required for the subjects to be included. Pelvic pain is assessed using a standardized questionnaire, and a visual analogue scale, quality of life using SF-36. The two groups are compared for the incidence and the severity of pelvic pain and for the impairment of their quality of life. RESULTS: Forty-seven patients have a minimal disease, whereas 111 have a severe endometriosis. Demographic characteristics are similar in both groups. Quality of life (SF-36) and pelvic pains included chronic pelvic pain, dyspareunia, dysuria, and defecation disorders are as common and severe in both groups. However, dysmenorrhea is more affected in group B than in group A (p=0.03). DISCUSSION AND CONCLUSION: We find no relationship between severity of symptoms, quality of life, and the extent of endometriotic lesions at surgery. There would be no differences between minimal and severe disease. It could be explained by different painful mechanisms between minimal and severe endometriosis.

[Endometrioma and management by assisted reproductive technology: CNGOF-HAS Endometriosis Guidelines]. / Endométriome et prise en charge en FIV, RPC Endométriose CNGOF-HAS.

Could the presence of an endometrioma change the management of Assisted Reproductive Technology? The presence of an endometrioma (<6cm) at the time of stimulation or an endometrioma operated prior to stimulation have no impact on the quality of the embryos and the final results of IVF about the pregnancy and live birth rates despite a possible decrease in the number of oocytes retrieved and potentially higher doses of gonadotropins used. The discovery of an endometrioma during IVF stimulation should not lead to an interruption of the attempt. Their surgical treatment before IVF is not recommended just to improve fertility. It is discussed in case of painful symptomatology, depending on the size and/or in case of diagnosis doubt. The associated indications for ART management and surgical history for endometrioma should also be taken into account. There is no benefit of prophylactic surgery to decrease the risk of tubo-ovarian abscess post ovarian retrieval. It is not recommended to make a systematic trans-vaginal ultrasound guided aspiration with or without sclerotherapy of endometriomas before IVF in order to increase pregnancy rates, but it is reserved in case of endometrioma that may hinder the oocyte retrieval. Ethanol sclerotherapy decreases the recurrence rate of endometriomas without altering the results of IVF while a second surgery would have a deleterious effect.

[Management by assisted reproductive technology in women with endometriosis: CNGOF-HAS Endometriosis Guidelines]. / Prise en charge en FIV en cas d'endométriose, RPC Endométriose CNGOF-HAS.

Should the presence of endometriosis change the management of assisted reproductive technology? There is no difference in pregnancy rate after IVF between an agonist or antagonist protocol in patients with endometriosis, so the choice between one or the other of these protocols is free. But the review of the literature has shown an improvement in the chances of pregnancy in case of prolonged ovulation suppression before stimulation for IVF with a GnRH agonist analogue or with oral contraception, especially in cases of severe endometriosis. Endometriosis, regardless of the stage and type of lesions, would have no effect on the IVF results in terms of pregnancy rate and live birth rate, but with a lower number of oocytes collected, especially in cases of severe endometriosis. In a context of superficial endometriosis without pain and of infertility, surgical treatment of superficial endometriosis is not recommended just to increase the chances of pregnancy in IVF. Surgery may have a place in case of failure of IVF to improve the results of the ART. In case of recurrence of endometriosis, surgery is not better than IVF, a medico-surgical concertation is recommended. In addition, studies on ovulation stimulation for IVF do not show any aggravation of the symptoms associated with endometriosis lesions, or an acceleration of its progression, or an increase in the rate of recurrence of the disease.

[Deeply infiltrating endometriosis and infertility: CNGOF-HAS Endometriosis Guidelines]. / Endométriose profonde et infertilité, RPC Endométriose CNGOF-HAS.

Deeply infiltrating endometriosis is a severe form of the disease, defined by endometriotic tissue peritoneal infiltration. The disease may involve the rectovaginal septum, uterosacral ligaments, digestive tract or bladder. Deeply infiltrating endometriosis is responsible for disabling pain and infertility. The purpose of these recommendations is to answer the following question: in case of deeply infiltrating endometriosis associated infertility, what is the best therapeutic strategy? First-line surgery and then in vitro fertilization (IVF) in case of persistent infertility or first-line IVF, without surgery? After exhaustive literature analysis, we suggest the following recommendations: studies focusing on spontaneous fertility of infertile patients with deeply infiltrating endometriosis found spontaneous pregnancy rates about 10%. Treatment should be considered in infertile women with deeply infiltrating endometriosis when they wish to conceive. First-line IVF is a good option in case of no operated deeply infiltrating endometriosis associated infertility. Pregnancy rates (spontaneous and following assisted reproductive techniques) after surgery (deep lesions without colorectal involvement) varie from 40 to 85%. After colorectal endometriosis resection, pregnancy rates vary from 47 to 59%. The studies comparing the pregnancy rates after IVF, whether or not preceded by surgery, are contradictory and do not allow, to date, to conclude on the interest of any surgical management of deep lesions before IVF. In case of alteration of ovarian reserve parameters (age, AMH, antral follicle count), there is no argument to recommend first-line surgery or IVF. The study of the literature does not identify any prognostic factors, allowing to chose between surgical management or IVF. The use of IVF in the indication "deep infiltrating endometriosis" allows satisfactory pregnancy rates without significant risk, regarding disease progression or oocyte retrieval procedure morbidity.

[Nerve sparing techniques in deep endometriosis surgery to prevent urinary or digestive functional disorders: Techniques and results: CNGOF-HAS Endometriosis Guidelines]. / Les techniques de préservation nerveuse dans la chirurgie de l'endométriose profonde pour prévenir les séquelles fonctionnelles urinaires et digestives : modalités techniques et résultats. RPC Endométriose CNGOF-HAS.

OBJECTIVES: To evaluate the feasibility and functional urinary and digestive results of nerve sparing techniques in endometriosis surgery. METHODS: A research on the medline/pubmed database using specific keywords (nerve sparing, endometriosis, pelvic nerves) identified 7 publications among about 50 whose purpose was to describe the feasibility, the techniques and the functional results of nerve preservation in this indication. Among them there are: 2 uncontrolled retrospective studies, 3 prospective non-randomized studies, a meta-analysis and a review of the literature. RESULTS: Nerve preservation requires a perfect knowledge of the anatomy of the pelvic autonomic system. The laparoscopic approach is preferred by the different authors due to its anatomical advantage. The feasibility of this technique seems to be demonstrated despite certain limitations in the different studies and depending of the retroperitoneal extension of the lesions. When feasible, it is likely to significantly improve postoperative urinary function (urinary retention) compared to a conventional technique. It is observed no difference regarding digestive function. CONCLUSIONS: Nerve sparing in this indication is a technique the feasibility of which has been demonstrated and is subject to the topography and extent of the disease. In the absence of invasion or entrapment of pelvic autonomic nerves by endometriosis, this technique improves postoperative voiding function (NP3). During pelvic surgery for endometriosis, it is recommended to identify and preserve autonomic pelvic nerves whenever possible (GradeC).

[Management of assisted reproductive technology (ART) in case of endometriosis related infertility: CNGOF-HAS Endometriosis Guidelines]. / Stratégies de prise en charge de l'infertilité en assistance médicale à la procréation dans un contexte d'endométriose, RPC Endométriose, CNGOF-HAS.

The management of endometriosis related infertility requires a global approach. In this context, the prescription of an anti-gonadotropic hormonal treatment does not increase the rate of non-ART (assisted reproductive technologies) pregnancies and it is not recommended. In case of endometriosis related infertility, the results of IVF management in terms of pregnancy and birth rates are not negatively affected by the existence of endometriosis. Controlled ovarian stimulation during IVF does not increase the risk of endometriosis associated symptoms worsening, nor accelerate the intrinsic progression of endometriosis and does not increase the rate of recurrence. However, in the context of IVF management for women with endometriosis, pre-treatment with GnRH agonist or with oestrogen/progestin contraception improve IVF outcomes. There is currently no evidence of a positive or negative effect of endometriosis surgery on IVF outcomes. Information on the possibilities of preserving fertility should be considered, especially before surgery.

[Are French results in assisted reproductive techniques so bad?]. / Résultats de l'Assistance médicale à la procréation en France: sommes-nous si mauvais?

OBJECTIVE: Comparative analysis of French results in Assisted Reproductive Techniques (ART) versus those from other European countries and the United States. POPULATION AND METHODS: The study was achieved by using the officially available data. The analysis was faced with a lot of difficulties in relation with the various methods of collecting data in the different countries. RESULTS: Nevertheless, it appears clearly that French results are among the lowest in Europe with a 22% rate for pregnancy per ovum pick-up with IVF and 23.4% with ICSI, when most of the other countries report rates that are close to or over 30%. Neither the patients' pick-up recruitment nor specific practices of ART can explain this difference that certainly comes from a deficient quality of the French IVF centres. DISCUSSION AND CONCLUSION: We think that four main end-points can explain this situation: the lack of financial support, the lack of human force, the lack of transparency and finally the opposition between clinician and biologist that has blocked the set-up of integrated ART centres, and probably a poor quality culture.

[Endometriosis related infertility]. / La stérilité par endométriose.

From the literature, the crucial knowledge were drawn among endometriosis related infertility. Endometriosis is an important factor of infertility in minimal or light stages and a major one in mild or moderate stages. Thus, a laparoscopy must be performed to confirm endometriosis when suggestive clinical or biological signs exist. In absence of them, laparoscopy can be delayed after intra-uterine inseminations (IUI). The first line treatment is laparoscopic surgery. Its efficacy is proven. It is useless to prescribe a post-operative medical treatment (GnRH analogues). Surgery leads to 25 to 40% of deliveries. It is dependant on age, infertility duration, tubo-ovarian adhesion and tubes involvement. But, surgery can be avoided and the patient is directly referred to In Vitro Fertilization (IVF) when the lesions extension is so important that surgery exposes to complications or when there is a permanent other indication for IVF (severe male infertility). When infertility persists 6 to 12 months after surgery and without patent recurrence, ovulation stimulations and IUI are performed as the second line treatment. After IUI failure, or in case of recurrence, IVF must be applied. A second surgery is not recommended. The IVF results are not impaired by the presence of endometriosis and even of endometriomas. Thus, it is useless to operate again endometriosis before IVF. In opposition, in severe stages or in cases of recurrence, a pre-IVF medical treatment (GnRH analogues) improves the results. IVF do not increased the risk of endometriosis acute growth. In case of infertility and pain, infertility is considered as the first target. But medical treatment can be prescribed between the IVF attempts.

SF-36 preoperative interest of predicting improvement of quality of life after laparoscopic management of minimal endometriosis.

THE PURPOSE OF THE STUDY: To study preoperative thresholds of the SF-36 components above which we can predict a high risk of failure in order to improve the quality of life after surgery for patients with minimal endometriosis. MATERIAL AND METHODS: Design: prospective and multicenter observational study between February 2004 and 2011. PATIENTS: 167 patients with operated minimal endometriosis. SETTING: for the Physical Component Summary (PCS) or the Mental Component Summary (MCS) subscales of the SF-36 questionnaire, an improvement defined by an increase of 5 points. INTERVENTION: evaluation by the SF-36 questionnaire the week before and one year after surgery. MEASUREMENT AND MAIN RESULTS: Success of surgery measured by an improvement in both components. We found significantly different initial variables between patients with improvement and those without: initial MCS score (P=0.0003), initial PCS score (P<0.0001) and dyspareunia (P=0.004). Multivariate analysis revealed only two significant variables. Initial MCS higher than 40 (OR=4.6) and initial PCS higher than 50 (OR=10.6) are risk factors for failure of improvement after surgery. CONCLUSION: Surgery is seldom a good treatment for improving QOL in minimal endometriosis. We set two thresholds for SF-36, 50 for PCS and 40 for MCS: above there is a very high risk of failure (86% of failure in our population). Under, the risk of failure remains high (54.3%). CANADIAN TASK FORCE CLASSIFICATION OF STUDY DESIGN: Evidence obtained from well-designed cohort or case-control studies, preferably from more than one center or research group.

[Laparoscopic promontal fixation: assessment of 100 cases]. / Promontofissazione laparoscopica: valutazione di 100 casi.

AIM: Aim of the study is to evaluate long term results of 100 patients treated laparoscopically to repair genital prolapse and urinary incontinence. METHODS: A retrospective review analysis of 100 women, who underwent laparoscopic genital prolapse repair at Primary Referral University Hospital in Clermont-Ferrand. Patients characteristics, preoperatory exams, intraoperative, postoperative and outpatient clinic data were collected and analyzed. RESULTS: The mean operative time was 172 minutes. One laparotomy conversion was required, due to a technical problem. The mean hospitalization stay was 4.7 days. Two patients required a reintervention during their hospitalization stay, due to a complication. All the patients were reviewed during the 6 months later the intervention. The follow-up is between 6 months and 3 years. The average degree of cystocele and hysterocele was ameliorated from stage 3 to stage 0, the average stage of rectocele was ameliorated from stage 2 to stage 0, finally the average stage of vault prolapse was ameliorated from stage 1 to stage 0. The incidence of genuine stress incontinence was 47% in the preoperative time and only 4% at the long follow-up. We had a total 4% rate of mesh vaginal erosion. CONCLUSIONS: The laparoscopic sacrocolpopexy is an effective and safe technique to repair the major pelvic prolapses.

[Transparency of results in assisted reproductive technology]. / Transparence des résultats en Assistance médicale à la procréation.

Clear results in ART need to take into account the technical performances of the centre but also patients selection, cycles cancelling and embryo transfer policies. The risk of a partial transparency is an inappropriate selection of patients. From classical criterias like pregnancies per oocytes retrievals or embryo transfers we are heading towards more global indicators like live births of singletons by initiated cycles rate.