Case Report of an exceptional spontaneous abdominal heterotopic pregnancy with superfetation: Diagnosis and treatment: Heterotopic pregnancy with superfetation (8+1 WG & 5+4 WG).

Heterotopic pregnancy is an extremely rare condition in which an intrauterine and an extrauterine pregnancy co-exist. In spontaneous conceptions, heterotopic pregnancy occurs in only 1/30 000 pregnancies. The treatment of heterotopic pregnancy must be as minimally invasive as possible to preserve the development of the intrauterine pregnancy. Superfetation, defined as the coexistence of 2 or more foetuses of different gestational ages, remains particularly exceptional and poorly explained (second ovulation? embryonic diapause?). Here, we present an extremely rare case of a spontaneous heterotopic evolutive pregnancy with superfetation, consisting of an embryo in the pouch of Douglas estimated at 8 + 1 weeks of gestation (WG) and a progressive intrauterine pregnancy estimated at 5 + 4 WG. We treated the extrauterine pregnancy with an intra-cardiac injection of potassium chloride echo-guided via the vaginal route, and the patient then underwent exploratory laparoscopy 9 days later and lavage and aspiration of the abdominal heterotopic pregnancy due to pain and biological inflammatory syndrome probably caused by pelvic mass syndrome and peritoneal irritation from the foetal necrosis. She has not yet given birth and is currently at 36 WG.

Assessment of female fertility preservation in Auvergne 3 years after implementation of the PREFERA platform (PREservation FERtilité Auvergne).

INTRODUCTION: Fertility preservation (FP) in patients with cancer or pathology at risk of gonadotoxicity is now according to legislation, an integral part of the treatment protocol. for this reason, clinical-biological platforms have emerged with the aim of developing and improving this practice, such as the PREFERA platform (PREservation FERtilité Auvergne) MATERIAL ET METHOD: This is an observational cohort study to evaluate female fertility preservation activity in Auvergne at the AMP-CECOS center of the Clermont-Ferrand University Hospital from March 2013 to March 2019. This period covering 3 years before and after the creation of PREFERA in 2015. RESULTS: 205 patients were referred for fertility preservation consultations, including 77 before the platform was set up and 128 after, corresponding to an increase of 66%. 190 patients (92.7%) referred were eligible for FP, of whom 169 (88.9%) received treatment. Thirty-nine patients underwent oocyte vitrification before the platform was set up and 74 after (+89.7%), twenty patients underwent ovarian cortex freezing before the platform was set up and 27 after (+35%). Only 54 patients (26.2%) were seen for follow-up with an increased number of consultations following the implementation of PREFERA. (8% vs 33%, p<0.001). CONCLUSION: Creation of the PREFERA platform facilitated patient access and management of fertility preservation procedures. However, at the regional level, it is necessary to continue to raise awareness of fertility issues, particularly in the context of post-cancer follow-up, both among patients and health professionals.

[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.

Pelvic adhesions and fertility: Where are we in 2018?

Peritoneal adhesions remain a major public health problem despite the development of laparoscopy. The rules of microsurgery must be known and followed during any pelvic surgery, even in patients who no longer have a desire for pregnancy. Anti-adhesion products are numerous. All have interest, confirmed by anatomical studies showing a smaller extent or a lesser severity of adhesions associated with their use. No studies, however, show clinical benefit in terms of improved pain or postoperative fertility. Pneumoperitoneum parameters, humidification, and lower abdominal pressure should be optimized to limit peritoneal trauma. Peri-operative corticosteroids, whose benefit has been has been demonstrated in at least one randomized trial, should be systematically used.

[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.

[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.

Trauma and endometriosis. A review. May we explain surgical phenotypes and natural history of the disease?

OBJECTIVE: The study was performed to evaluate whether trauma is an initial event of development of endometriosis. METHOD: Using Medline database from January 1960 up to December 2014, a systematic review was made of all published studies using the keywords trauma, healing, injury, infection, hyperperistaltism, stretch and endometriosis, adenomyosis and trauma. Studies and review articles written in French and/or in English related to the topic were included and reviewed independently by two authors. RESULTS: The role of trauma is well-established for endometriotic lesions diagnosed in surgical scars. Various traumas including delivery, uterine curettage or incision, intraperitoneal hemorrhage, or occult pelvic inflammatory diseases could be involved to explain other localizations of the disease. Many data suggested that the healing process, particularly growth factors and the associated estrogen production, may facilitate the implantation and the growth of ectopic endometrial cells. After the initial, a traumatic event, the phenotype of the disease would depend on the tissue in which the endometriotic lesion grows. CONCLUSIONS: The present literature review may support a potential role of a trauma as an initial event of endometriosis.

[PRESERVING FERTILITY AND FUTURE DEATH]. / PRÉSERVATION DE LA FERTILITÉ ET LA MORT À VENIR: UNE DOUBLE PEINE?

The fertility preservation when it is threatened is a right enshrined in the french law on bioethics. It is most often performed before gonadotoxic treatments for cancers with a long survival. When the patient has a limited life expectancy, is the preservation of fertility lawful? The authors present the arguments for and against the preservation of fertility in this particular situation and give driving they adopt in their team.

[Adverse pregnancy outcomes after Assisted Reproduction Technology in women with endometriosis]. / Issues obstétricales des grossesses obtenues par Assistance médicale à la procréation chez les femmes endométriosiques.

OBJECTIVE: While association between endometriosis and infertility is well established, there are few studies about the impact of endometriosis on adverse pregnancy outcomes. The aim of this study was to determine the effect of endometriosis on obstetric outcomes and whether the severity of the disease had an influence on these. PATIENTS AND METHODS: We performed a retrospective study to investigate the obstetric outcomes of a population of 1204 subfertile women, including 258 with endometriosis, who obtained, thanks to assisted reproduction technology, a singleton pregnancy evolving beyond embryonic stage. Two analyzes were performed. The first compared women with endometriosis to women with other causes of infertility. The second observed adverse pregnancy outcomes according to AFS-R stages of endometriosis. RESULTS: The overall rate of live birth children was 95.8%. In case of endometriosis, there was a significant increase of the incidence of preterm delivery, especially before 32 weeks amenorrhea (6.2% vs 3.1% in the group "without endometriosis", P = 0.03), antenatal bleeding (5.3% vs 2.2%, P = 0.01) and placenta previa (4.9% vs 0.9%, P < 0.0001). The incidence of gestational diabetes was significantly decreased (0.4% vs 2.7%, P = 0.04). There was no correlation between endometriosis and cesarean section or preeclampsia, or between the AFS-R stage and adverse pregnancy outcomes. DISCUSSION AND CONCLUSION: Endometriosis is a factor of obstetrical risk, independently of the infertility it causes. The AFS-R score does not seem to be representative of obstetric outcomes beyond first trimester of pregnancy for women with endometriosis.

[Ovarian drilling by fertiloscopy: feasibility, results and predictive values]. / Drilling ovarien par fertiloscopie : faisabilité, résultats et valeurs prédictives.

OBJECTIVES: The aims of this study were to assess the effectiveness of the ovarian drilling, compare the techniques by fertiloscopy or by laparoscopy, and search for prognostic factors of success. PATIENTS AND METHODS: This retrospective study focused on 154 ovarian drilling carried out between June 1998 and December 2010 where the drilling has been proposed after failure of the clomifene and before stimulation by FSH among PCOS patients. RESULTS: The post-drilling ovulation rate is 62%. The spontaneous on-going pregnancy rate is 31% and the total pregnancy rate scalable including secondary stimulation is 58%. No significant difference was found between laparoscopy and the fertiloscopy. The peroperative complications in fertiloscopy were more frequent but without consequences and 20% of the fertiloscopy had to be converted to laparoscopy, half of them for complications and half of them for technical difficulties. The only found preoperative predictors of success are an euthyroidy that increases the chances of pregnancy in general (including the side stimulation) and a lower FSH levels. However, it appears that the chances of pregnancy in FSH stimulation are dramatically decreased if the drilling did not induce ovulation versus the cases where it induced ovulation but no pregnancy (28.8% versus 58.1%, P<0.003). DISCUSSION AND CONCLUSION: Fertiloscopy results are comparable with those of laparoscopy, which suggests an advantage to this technique in terms of cost, comfort, and length of hospital stay. No usable in practice patient selection criteria could be highlighted. The study suggests that the absence of ovulation after drilling may be a direct indication for IVF.

[Reduction of multiple pregnancies in ART with large SET procedures over the period 2001-2010]. / Réduction des grossesses multiples en AMP par un usage large du SET (Single Embryo Transfer) sur la période 2001-2010.

OBJECTIVE: To evaluate delivery rate and multiple pregnancy rates in ART (assisted reproductive techniques) following introduction of an elective single embryo tranfer (eSET) policy. This strategy was started in 2002 including transfer of one embryo for women less than 35 years with a least two good quality embryo during their first or second attempts. PATIENTS AND METHODS: Retrospective study including all IVF cycles performed in the IVF centre of Clermont-Ferrand University Hospital from 01/01/2001 to 31/12/2010. Main outcome measures were number of embryos transferred, cumulative delivery and multiple pregnancy rates (including fresh and frozen embryo transfers). A subgroup analysis including patients' age was done. RESULTS: Cumulative delivery rate reached 27,3% in 2010 with a significant drop in multiple pregnancy rate: from 30% in 2001 to 7,9% in 2010. The average number of transferred embryo decreased from 2.29 to 1.55 in the same period. In our centre, eSET was performed in 85% of first IVF attempt and in 34,4% of second attempts for women less than 35 years. CONCLUSION: The implementation of an eSET policy does not change the delivery rate but significantly decrease the number of multiple pregnancies compared to double embryo transfer. eSET should be carried out during the 1st and 2nd attempts in patients under 35 years when at least two good quality embryos were obtained.

[Factors affecting the cumulative live birth rate in IVF cycles. Retrospective analysis of a 1001 couples cohort]. / Analyse des facteurs influençant les taux cumulatifs d'accouchement en AMP sur une cohorte de 1001 couples.

OBJECTIVE: To analyze the different factors influencing real and theoretical cumulative live birth rates following in vitro fertilization. PATIENTS AND METHODS: Retrospective study of 1001 couples starting an IVF/ICSI cycle between 2004 and 2006 that were followed-up after all their attempts. All abandoned cycles were taken in account. RESULTS: For all couples, the theoretical cumulative live birth rates after n attempts were 23.9%, 40.5%, 51.4%, 62.2%. The real cumulative live birth rates were 23.9%, 36%, 41.2% and 44.4%. With reference to age, success rates were better for women less than 35 (58,8%) and were reduced for women older than 38 (18,0%). Looking at the ovarian reserve, in the 35 to 38 years age group, the actuarial rates were satisfactory as long as the ovarian response resulted in five or more oocytes. Among older patients, success rates were influenced by the number of oocytes collected and only acceptable when more than eight oocytes were obtained. Multivariate analysis has demonstrated that women's age was determinant on the live birth rate (OR=0.17 [0.09-0.32] in the 38 to 39 group versus less than 30 group). In ovulatory disease, the success rates were the best compared to other infertility aetiology (OR=1.61[1.05-2.47]). Moreover, the number of embryos transferred had a strong impact on live birth rate with an OR of 1.62 [1.32-1.99] per extra embryo. DISCUSSION AND CONCLUSION: Live birth rates are dependent on the women' age. For women older than 38 years, the ovarian response to the stimulation and the number of embryos transferred are important factors for success.

Outcome and feasibility of elective single embryo transfer (eSET) policy for the first and second IVF/ICSI attempts.

OBJECTIVE: This study assesses the outcome and the feasibility of an elective single embryo transfer (eSET) policy for the first and second IVF/ICSI attempts. STUDY DESIGN: This is a retrospective analysis performed on 611 couples attempting a first IVF cycle in Clermont-Ferrand University Hospital, France. eSET was offered to the couples when they had 2 embryos with at least one of good quality at day 2 for their first and second IVF/ICSI cycles. RESULTS: Among the couples selected for the study, 442 underwent an eSET and 341 a double embryo transfer (DET). The cumulative ongoing pregnancy rate (OPR) and the cumulative delivery rate (DR), including fresh and frozen embryo transfer, did not differ statistically between the two groups, respectively 40.7% and 30.9% in the eSET group and 42.5% and 34.6% in the DET group. The twin pregnancy rate was lower in the eSET group (0.7% vs. 21.2%; p<0.0001) and neonatal and obstetrical outcomes were better than in the DET group. For the first attempt, the global twin rate (including eSET and DET) was 7.1% and the proportion of eSET was high, 67.6%, but for the second attempt the eSET rate was only 16.9%, with an increased global twin rate of 21.4% (p=0.042). CONCLUSION: In a selected population an eSET strategy decreases the twin pregnancy rate without decreasing the delivery rate, with a better outcome for the infants than DET. However, eSET is well accepted by patients only for the first attempt even though the pregnancy rate is not statistically different for the second.

[Outcome of elective single or double embryo transfer in first and second IVF/ICSI cycles]. / Comparaison des résultats du transfert électif d'un ou de deux embryons lors des premières et secondes tentatives de FIV/ICSI.

BACKGROUND: The aim of the study is to compare the incidence of eSET (elective single embryo transfer) and DET (double embryo transfer) and their results about live birth and twin pregnancies between first and second IVF/ICSI cycles, in a selective population. These data allow analysing whether the extension of elective single embryo transfer in the second cycle is efficient. PATIENTS AND METHODS: Retrospective study about embryo transfers performed in first and second IVF/ICSI cycles in the IVF unity (CHU Clermont-Ferrand) between 1 January 2004 and 31 December 2006. Women belonging to couples considered have less than 36 years. On the second day of embryo development, at least two good quality embryos have been observed. After information about eSET and DET, couples give their written consent to the transfer of one or two embryos. Couples who have no live birth at the end of the first cycle have been followed up for the second cycle whether they correspond to the inclusions criteria. Analysis is performed with live birth rates by tentative (overall rate) and after one or two embryo transfer, cumulative live birth rate (including fresh and frozen embryo transfer, and twin pregnancy rate. RESULTS: An embryo transfer at the first IVF/ICSI cycle (report eSET/DET=0.5) has been performed for 513 patients. The overall cumulative live birth rate is 37.1%, without significant difference between eSET and DET (36.2% vs 35.7%, p=ns). The twin pregnancies rate is 12% (including 0% in eSET vs 24% in DET, p<0001). Two hundred and five patients have a second IVF/ICSI cycle (92.3% in DET and 7.7% in eSET). The overall cumulative live birth rate is 34.1% without difference between eSET and DET (31.3% vs 34.3%). The twin pregnancies rate is 22.5% and it is significantly higher compared with the first attempt (including 0% in ESET and 24.6% in DET). DISCUSSION AND CONCLUSION: The increased twin pregnancies rate during the second cycle is explained by the higher rate of DET. This may be explained by the non-acceptance by couples of a new eSET, despite acceptable results for live birth rate. We have to search for solutions to encourage its development like the reimbursement of more cycles when eSET is performed, or with regulations as in Belgium, because the information to the couples is not efficient.

[Results in assisted reproductive techniques: interpretation and function]. / Interprétation et finalité des résultats en Assistance médicale à la procréation.

The modes of expression in assisted reproductive techniques are numerous. The delivery rate per started cycle must include the deliveries issued of thawed embryos transfer. The birth rates per patient are a different modality of great interest for the crude as well as the actuarial cumulative delivery rates. But all these data should be interpreted within their context: selection of patients or health policy. The disparity of expression of results comes from the function of these results. Scientific analysis, public health, monitoring quality and prognostic value are the four main purposes justifying differentiated expression modes.