Cervical Cancer Associated with Pregnancy: Current Challenges and Future Strategies.

Cancer during pregnancy is defined as a tumor diagnosed in a pregnant woman or up to 1-year post-partum. While being a rare disease, cervical cancer is probably one of the most challenging medical conditions, with the dual stake of treating the cancer without compromising its chances for cure, while preserving the pregnancy and the health of the fetus and child. To date, guidelines for gynecological cancers are provided through international consensus meetings with expert panels, giving insights on both diagnosis, treatment, and obstetrical care. However, these expert guidelines do not discuss the various approaches than can be found within the literature, such as alternative staging modalities or innovative surgical approaches. Also, the obstetrical care of women diagnosed with cervical cancer during pregnancy requires specific considerations that are not provided within our current standard of care. This systematic review aims to fill the gap on current issues with regards to the management of cervical cancer during pregnancy and provide future directions within this evolving landscape.

Second-trimester medical abortion after exposure to lorlatinib during early pregnancy, a case report.

Use of Lorlatinib, a third-generation tyrosine kinase inhibitor currently indicated in the treatment of non-small-cell lung cancer (NSCLC) with ALK or ROS1 gene fusion, is formally contra-indicated during pregnancy due to teratogenic effects observed during pre-clinical studies. We report the case of a 38-year-old woman with a ROS1-positive NSCLC, successfully treated with lorlatinib as second line therapy, who became pregnant while on treatment. Due to significant disease progression 12 weeks after lorlatinib stop and the great uncertainty on the pregnancy outcome, she finally decided to interrupt the pregnancy at 22 weeks of gestation. Echography and gross infant examination did not reveal any malformation. Pregnancies occurring under this kind of new oncologic treatment is expected to happen more frequently in the future. It seems therefore important to us to report any information on the topic to increase our level of knowledge and improve decision-making.

A Machine Learning Approach for the Prediction of Testicular Sperm Extraction in Nonobstructive Azoospermia: Algorithm Development and Validation Study.

BACKGROUND: Testicular sperm extraction (TESE) is an essential therapeutic tool for the management of male infertility. However, it is an invasive procedure with a success rate up to 50%. To date, no model based on clinical and laboratory parameters is sufficiently powerful to accurately predict the success of sperm retrieval in TESE. OBJECTIVE: The aim of this study is to compare a wide range of predictive models under similar conditions for TESE outcomes in patients with nonobstructive azoospermia (NOA) to identify the correct mathematical approach to apply, most appropriate study size, and relevance of the input biomarkers. METHODS: We analyzed 201 patients who underwent TESE at Tenon Hospital (Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris), distributed in a retrospective training cohort of 175 patients (January 2012 to April 2021) and a prospective testing cohort (May 2021 to December 2021) of 26 patients. Preoperative data (according to the French standard exploration of male infertility, 16 variables) including urogenital history, hormonal data, genetic data, and TESE outcomes (representing the target variable) were collected. A TESE was considered positive if we obtained sufficient spermatozoa for intracytoplasmic sperm injection. After preprocessing the raw data, 8 machine learning (ML) models were trained and optimized on the retrospective training cohort data set: The hyperparameter tuning was performed by random search. Finally, the prospective testing cohort data set was used for the model evaluation. The metrics used to evaluate and compare the models were the following: sensitivity, specificity, area under the receiver operating characteristic curve (AUC-ROC), and accuracy. The importance of each variable in the model was assessed using the permutation feature importance technique, and the optimal number of patients to include in the study was assessed using the learning curve. RESULTS: The ensemble models, based on decision trees, showed the best performance, especially the random forest model, which yielded the following results: AUC=0.90, sensitivity=100%, and specificity=69.2%. Furthermore, a study size of 120 patients seemed sufficient to properly exploit the preoperative data in the modeling process, since increasing the number of patients beyond 120 during model training did not bring any performance improvement. Furthermore, inhibin B and a history of varicoceles exhibited the highest predictive capacity. CONCLUSIONS: An ML algorithm based on an appropriate approach can predict successful sperm retrieval in men with NOA undergoing TESE, with promising performance. However, although this study is consistent with the first step of this process, a subsequent formal prospective multicentric validation study should be undertaken before any clinical applications. As future work, we consider the use of recent and clinically relevant data sets (including seminal plasma biomarkers, especially noncoding RNAs, as markers of residual spermatogenesis in NOA patients) to improve our results even more.

Stimulation Duration in Patients with Early Oocyte Maturation Triggering Criteria Does Not Impact IVF-ICSI Outcomes.

Results from studies reporting the optimal stimulation duration of IVF-ICSI cycles are inconsistent. The aim of this study was to determine whether, in the presence of early ovulation-triggering criteria, prolonged ovarian stimulation modified the chances of a live birth. This cross-sectional study included 312 women presenting triggering criteria beginning from D8 of ovarian stimulation. Among the 312 women included in the study, 135 were triggered for ovulation before D9 (D ≤ nine group) and 177 after D9 (D > nine group). The issues of fresh +/− frozen embryo transfers were taken into consideration. Cumulative clinical pregnancy and live-birth rates after fresh +/− frozen embryo transfers were similar in both groups (37% versus 46.9%, p = 0.10 and 19.3% versus 28.2%, p = 0.09, respectively). No patient characteristics were found to be predictive of a live birth depending on the day of ovulation trigger. Postponing of ovulation trigger did not impact pregnancy or live-birth rates in early responders. A patient's clinical characteristics should not influence the decision process of ovulation trigger day in early responders. Further prospective studies should be conducted to support these findings.

Prognosis of triple-negative breast cancer associated with pregnancy: A propensity score-matched analysis from the French CALG (Cancer Associé à la Grossesse) network.

INTRODUCTION: Triple-negative (TN) breast cancer represents one third of pregnancy-associated breast cancers (PABC). The aims of the current study were to describe oncological and obstetrical outcomes of patients with TN-PABC and to compare their prognosis with TN-non-PABC patients using a propensity score. MATERIALS AND METHODS: Between January 2005 and December 2020, data of patients with histologically proven TN-PABC were collected and compared with data of TN-non-PABC patients under the age of 46 years diagnosed during the same period using a propensity score (PS). RESULTS: After PS matching (tumor size and lymph node involvement),there were 59 patients in each group. The median follow-up was 14 months (IQR 4.8-40.1) for the TN-PABC group and 60 months (IQR 30.7-101.4) for the TN-non-PABC group. Eight recurrences occurred in the TN-PABC group and 10 in the TN-non-PABC group (adjusted OR (AOR) = 0.60 (0.21-1.60), HR (Cox adjusted model- AHR) = 1.25 (0.53-2.94)). Two patients died in the TN-PABC group, and six in the TN-non-PABC group with an AOR = 0.23 (0.03-1.01) and an AHR = 0.58 (0.12-2.69). All the patients diagnosed during the second (n = 17) and third trimesters (n = 28) continued their pregnancies, with a median term at delivery of 38 WG (IQR 36-39). All patients gave birth to healthy newborns. CONCLUSION: Although the TN subtype is associated with poor prognosis in pregnant patients due to advanced stage at diagnosis and high lymph node involvement, our PS-matched case-control study showed that pregnancy per se does not worsen the prognosis in terms of recurrence-free and overall survival.

Secondary infertility with a history of vaginal childbirth: Ready to have another one?

INTRODUCTION: Up to 30% of couples may face secondary infertility. The impact of ectopic pregnancy, spontaneous abortion, pregnancy termination or live birth with caesarean section may impair further fertility in different ways. However, secondary infertility after physiological vaginal life childbirth has been little studied. The aim of this study was to describe the population and the fertility issues and analyze the predictive factors of success in in vitro fertilization in women presenting secondary infertility after a physiological vaginal childbirth. MATERIAL AND METHODS: This single-centre retrospective study included women aged 18-43 years consulting between 2013 and 2020 for secondary infertility in a couple having already had previous vaginal life childbirth. Couples' characteristics, management decision after the first consultation and IVF outcomes were analyzed. RESULTS: Secondary infertility was found in 286 couples, out of whom 138 had a history of vaginal life childbirth. Population was characterized by an advanced female age and overweight. After the first consultation, IVF was performed in only 40% of couples. No predictive factor of live birth was found. CONCLUSION: Our study shows that in couples with secondary infertility after prior physiological delivery cigarette smoking is frequent in male partners, and ovarian reserve markers are altered. However, no statistically significant predictive factor of live birth after IVF treatment has been identified. Further large prospective studies are necessary.

Feasibility, Safety and Impact of (18F)-FDG PET/CT in patients with pregnancy-associated cancer: experience of the French CALG (Cancer Associé à La Grossesse) network.

BACKGROUND: The incidence of pregnancy-associated cancers has been increasing for decades. (18F)-FDG Positron Emission Tomography (PET)/Computed Tomography (CT) imaging has become a golden standard in the staging of many malignant diseases. The aims of the current study were to evaluate the feasibility, safety and impact of (18F)-FDG PET/CT performed during pregnancy. MATERIAL AND METHODS: A retrospective analysis from the prospective database of the Cancer Associé à La Grossesse (CALG) network (Tenon Hospital, France) including patients who underwent (18F)-FDG PET/CT during their pregnancy between 2015 and 2020. RESULTS: Of the 536 patients for whom advice from the CALG network was requested during the study period, 359 were diagnosed with cancer during pregnancy. Study population was composed of 63 (17.5%) patients who underwent (18F)-FDG PET/CT. Most cancers were diagnosed during the second trimester. Seventy-five percent were diagnosed with breast cancer, mostly locally advanced invasive ductal carcinomas. Median term of pregnancy at PET/CT was 24.8 weeks of gestation. Twelve (19%), 24 (38.1%) and 22 (34.9%) patients underwent the exam during the 1st, 2nd and 3rd trimester, respectively. (18F)-FDG PET/CT resulted in stage modification for 38 (60.3%) of the patients (28 with more extensive lymph node involvement and 10 with metastatic disease) with subsequently/accordingly modified first-line medical treatment. Fifty patients gave birth to healthy newborns. Two patients had a medical termination of pregnancy, five had a medical abortion, one neonatal death occurred in a patient with severe preeclampsia (unrelated to (18F)-FDG PET/CT). The data of 46 children were available at 6 months, 29 at 12 months, and 15 at 24 months. No cases of mental retardation, childhood cancer, or malformation were reported within 2 years. CONCLUSION: (18F)-FDG PET/CT has a major impact on the management of pregnancy-associated cancers and does not appear to cause fetal side effects suggesting that the exam is feasible during pregnancy as maternal benefits outweigh fetal risks.

Comparison of in vitro fertilization cycles in couples with human immunodeficiency virus type 1 infection versus noninfected couples through a retrospective matched case-control study.

OBJECTIVE: To compare in vitro fertilization (IVF) outcomes in couples in which at least one partner is human immunodeficiency virus (HIV) positive with that of couples in which neither partner is HIV-positive. DESIGN: Retrospective matched case-control study. SETTING: Fertility center at Tenon Hospital, Paris, France. PATIENTS: A total of 179 IVF cycles in couples infected with HIV-1 and 179 IVF cycles in control couples. INTERVENTIONS: Ovarian stimulation, oocytes retrieval, IVF (standard and microinjection), embryo transfer, pregnancy, and live birth follow-up. MAIN OUTCOME MEASURES: Live birth rate and IVF outcomes. RESULTS: The first comparison between HIV and non-HIV couples showed poorer outcomes in the HIV group (higher administered gonadotropin doses and longer stimulation periods, lower cumulative pregnancy and live birth rates, among other things). A subgroup analysis was performed in addition. No differences were found in the "men HIV" group compared with the controls. In contrast, poorer outcomes in the "women HIV" and "women and men HIV" groups were shown in terms of administered doses, duration of stimulation, and number of oocytes retrieved. For the "women HIV" group, lower cumulative clinical pregnancy and live birth rates were found. CONCLUSION: The data suggested that couples with HIV-positive women have poorer medically assisted procreation outcomes than couples with non-HIV-infected women. Therefore, physicians should pay particular attention to couples with HIV-positive women.

Use of tyrosine kinase inhibitors during pregnancy for oncogenic-driven advanced non-small cell lung carcinoma.

INTRODUCTION: Lung cancer associated with pregnancy is rare but on the increase. The use of tyrosine kinase inhibitor (TKI) therapy for advanced oncogenic-driven non-small cell lung carcinoma (NSCLC) has improved overall survival. Oncological and obstetric outcomes of patients diagnosed with NSCLC and treated by TKIs during pregnancy have been poorly evaluated. METHODS: Three cases of NSCLC treated by TKIs during pregnancy were collected from the prospective database of the Cancer Associé à La Grossesse (CALG) network (France) in addition to eight cases identified by a systematic review performed between 2000 and 2021. RESULTS: Among the eleven reported patients, six received an EGFR- and five an ALK-TKI. All patients were young nonsmokers and four had brain metastases at diagnosis. TKI treatment was initiated during the first trimester for three patients. Premature delivery was induced in 10/11 patients. Anamnios occurred in one patient treated by osimertinib and trastuzumab. Five newborns were hypotrophic. No newborn malformations were observed. Diffusion of the TKIs, confirmed by blood cord sampling, represented about 1/3 (EGFR-TKI) and 1/8 (ALK-TKI) of the maternal concentration. No developmental abnormalities were observed in the children (follow-up 30 months). The anti-tumor efficacy and tolerance of TKIs, when reported, appears similar to that described in the general population. CONCLUSIONS: Our results support the rationale for using TKIs during pregnancy, both in terms of maternal NSCLC disease control and the relatively mild effects on the fetus. Our data will serve to better inform patients about the risks associated with TKIs used during pregnancy, contributing to shared decision making.

Unexplained recurrent implantation failures: Predictive factors of pregnancy and therapeutic management from a French multicentre study.

INTRODUCTION: Recurrent implantation failure is defined as the absence of pregnancy after at least three transfers of good-quality embryos after in vitro fecundation/intracytoplasic sperm injection. AIM: The aim of this study was to describe a multicentre cohort of women with unexplained RIF, to analyse the factors associated with clinical pregnancy and to evaluate the immunomodulatory therapies efficacy. METHODS: Women were consecutively recruited from university departments with unexplained RIF. RESULTS: Sixty-four women were enrolled with mean age 36 ± 3 years. The rates of clinical pregnancy in 64 women were compared in untreated and treated cycles and according to therapies used during the last prospectively followed embryo transfer. A clinical pregnancy after the transfer was noted in 56 % pregnancies on intralipids and in 50 % on prednisone, versus 5 % in untreated ones (p < 0.001). The 340 embryo transfers of these 64 women resulted in 68 clinical pregnancies and 18 live births. Clinical pregnancies were significantly more frequent in treated versus untreated embryo transfers (44 % vs 9 %; p < 0.001) with odds ratio at 8.13 (95 % CI 4.49-14.72, p < 0.0001). Cumulative pregnancy rates were higher for steroid-treated transfers than for untreated transfers when considering overall transfers before and after using steroids and also only those under steroids. Cumulative pregnancy rates were not different from steroid- and intralipid-treated embryo transfers CONCLUSIONS: In this multicentre study of women with unexplained RIF, use of immunomodulatory treatments before embryo transfer resulted in higher clinical pregnancy. Randomised, well-designed studies in well-defined population of RIF women are necessary to confirm our preliminary data.

Unexplained recurrent miscarriages: predictive value of immune biomarkers and immunomodulatory therapies for live birth.

INTRODUCTION: Recurrent miscarriages are defined as three or more early miscarriages before 12 weeks of gestation. The aim of this study was to describe a cohort of women with unexplained recurrent miscarriages, evaluate several potential biomarkers of immune origin, and describe the outcome of pregnancies under immunomodulatory therapies. METHODS: Women having a history of at least 3 early miscarriages without any etiology were recruited from 3 university hospitals. RESULTS: Among 101 women with recurrent miscarriages, overall, 652 pregnancies have been included in the analysis. Women which experienced miscarriages were older (33.3 ± 5.4 versus 31.9 ± 6.7; p = 0.03), with history of more pregnancies (4 (2-6) versus 3.5 (1-5.75); p 0.0008), and less frequently the same partner (406 (74%) versus 79 (86%); p=0.01). There was no difference in the level and frequencies of biomarkers of immune origin (NK, lymphocyte, gamma globulins and blood cytokine levels and endometrial uNK activation status), except the higher rates of positive antinuclear antibodies in women with live birth (12 (13%) versus 36 (7%); p=0.03). Among the 652 pregnancies, 215 (33%) have been treated and received either aspirin/low weighted molecular heparin (LMWH) and/or combined to different lines of immunomodulatory treatment. Patients with pregnancy under treatment had a significantly higher rate of cumulative live birth rate than those with untreated ones (43.0% vs 34.8%; p = 0.04). When compared to patients with untreated pregnancies, patients with steroids during the pregnancy had twice more chances to obtain live birth (OR 2.0, CI95% 1.1 - 3.7, p = 0.02). CONCLUSIONS: Unexplained recurrent miscarriages could have improved obstetrical outcome under immunomodulatory therapies and in particular steroids.

Predicting the likelihood of recurrence of pregnancy-associated breast cancer: Nomogram based on analysis of the French cancer network: Cancer Associé à La Grossesse.

OBJECTIVE: Pregnancy associated breast cancer (PABC) are defined as breast cancer diagnosed during pregnancy and during the year following delivery. The prediction of poor prognosis events (PPE) such as recurrence is a major medical challenge of management for women with PABC. The aim of this study was to build a nomogram based on selected clinical and histological variables to predict recurrence. STUDY DESIGN: This retrospective study included 96 patients with PABC from January 2002 to January 2018. A multivariate Cox analysis of selected risk factors was performed and a nomogram to predict recurrence was built. The nomogram was internally validated. RESULTS: The overall recurrence rate was 22% (21/95) and the 3-years recurrence rate was 13% (12/95). Age at diagnosis, histological type, immuno-histological class, tumor stage (TNM), node stage (TNM) were associated with PPE in univariate analysis, and were included in the final Cox model to develop the nomogram. The predictive model had a concordance index of 0.83 (95% Confidence Interval (CI), 0.81-0.85) and 0.78 (95% CI, 0.76-0.80) before and after the 200 repetitions of bootstrap sample corrections, respectively, and showed a good calibration. CONCLUSION: Our results support the use of the present nomogram based on 5 clinical and pathological characteristics to predict PPE in PABC with a high concordance. External validation is required to recommend this nomogram in routine practice.

Endometriosis with infertility: A comprehensive review on the role of immune deregulation and immunomodulation therapy.

BACKGROUND: Endometriosis is a multifactorial pathology dependent on intrinsic and extrinsic factors, but the immune deregulation seems to play a pivotal role. In endometriosis-associated infertility, this could raise the benefit of immunomodulatory strategies to improve the results of ART. In this review, we will describe (1) sera and peritoneal fluid cytokines and immune markers; (2) autoantibodies; and (3) immunomodulatory treatments in endometriosis with infertility. METHODS: The literature research was conducted in MEDLINE, Embase, and Cochrane Library with the following keywords: "endometriosis", "unexplained miscarriage", "implantation failure", "recurrent implantation failure ¼ and « IVF-ICSI ¼, « biomarkers of autoimmunity", "TNF-α", "TNF-α antagonists", "infliximab", "adalimumab", "etanercept", "immunomodulatory treatment", "steroids", "intralipids", "intravenous immunoglobulins", "G-CSF", "pentoxyfylline". RESULTS: Several studies analyzed the levels of pro-inflammatory cytokines in sera and peritoneal fluid of endometriosis-associated infertility, in particular TNF-α. Various autoantibodies have been found in peritoneal fluid and sera of infertile endometriosis women even in the absence of clinically defined autoimmune disease, as antinuclear, anti-SSA, and antiphospholipid autoantibodies. In few uncontrolled studies, steroids and TNF-α antagonists could increase the pregnancy rates in endometriosis-associated infertility, but well-designed trials are lacking. CONCLUSION: Endometriosis is characterized by increased levels of cytokines and autoantibodies. This suggests the role of inflammation and immune cell deregulation in infertility associated with endometriosis. The strategies of immunomodulation to regulate these immune deregulations are poorly studied, and well-designed studies are necessary.

Prognosis of HER2-positive pregnancy-associated breast cancer: Analysis from the French CALG (Cancer Associé à La Grossesse) network.

INTRODUCTION: The prevalence of pregnancy-associated breast cancer is increasing. HER2-positive breast cancers typically have a poor prognosis. The objective of our study was to compare the prognosis of patients with HER2-positive breast cancer diagnosed during pregnancy (HER2-positive BCP) to young women diagnosed with HER2-positive breast cancer outside of pregnancy (HER2 non-BCP). METHODS: Data of patients managed for invasive breast carcinoma between January 2005 and 2020 were retrospectively collected from the database of Tenon University Hospital (Paris, France), part of the "Cancer lié à la Grossesse" network. RESULTS: Fifty-one patients with HER2-positive BCP were matched on age at diagnosis with 51 HER2-positive non-BCP patients. Locally advanced disease with axillary lymph node involvement were frequent. Tumors were frequently aggressive with high grade (p = 0.57) and high Ki67 (p = 0.15). Among the HER2-positive BCP patients, the mean term at diagnosis was 19.3 week of gestation (WG). Eighty-four percent of the patients continued their pregnancy with a mean term at delivery of 34.2WG. Chemotherapy modalities differed between the two groups: neoadjuvant chemotherapy was more frequent in the HER2-positive BCP group (p = 0.03) and adjuvant chemotherapy more frequent in the HER2 non-BCP group (p = 0.009). The recurrence rate was 10% (n = 5) and 18% (n = 9) in the HER2-positive BCP and HER2 non-BCP groups, respectively, p = 0.25. Breast cancer-free survival was poorer in the HER2-positive BCP group with earlier recurrence, p = 0.008. No difference in type of recurrence was found between the groups (p = 0.58). CONCLUSION: This matched case-control study implies that patients with HER2-positive BCP still have a poorer prognosis than non-pregnant HER-positive patients.

Oncological management of pregnancy-associated cancers: analysis from the French CALG (Cancer Associé à La Grossesse) network.

Background: Pregnancy-associated cancers constitute a major medical challenge. The objective of this study was to describe their epidemiological, oncological and obstetrical outcomes from the French CALG (Cancer Associé à La Grossesse) network.Material and methods: Retrospective analysis of patients diagnosed with a cancer associated with pregnancy between January 2015 and December 2018 after advice from the CALG network.Results: Of 218 patients, 197 (90%) were diagnosed with a cancer during pregnancy and 21 the year following delivery. Requests to the CALG network increased from 36 cases in 2015 to 77 cases in 2018. The disease was diagnosed at local and regional stages in 77% of cases. Breast cancer was the most frequent (56%), followed by ovarian (12%) and uterine cervical cancers (10%). Of the 218 patients, 157 (72%) underwent a treatment during pregnancy. Surgery and chemotherapy during pregnancy were performed in 83 patients (83/218, 38%) and 101 patients (46%) at a median term of 17 (IQR 11-24) and 25 (IQR 18-30) WG, respectively. Eighteen (8.5%) of the women had a pregnancy termination, two (1%) an abortion, one (0.5%) a miscarriage, one (0.5%) had a stillbirth and one (0.5%) patient died during pregnancy. The remaining 174 patients (88%) were allowed to continue the pregnancy. Eight recurrences and four deaths were observed with a median follow-up time of 2.6 years (IQR 2.2-3.8).Conclusions: Our data further describe the incidence and management of pregnancy-associated cancers in western Europe allowing comparisons with other regions.

Intralipid therapy for unexplained recurrent miscarriage and implantation failure: Case-series and literature review.

INTRODUCTION: In retrospective cohort study of women with unexplained recurrent implantation failure (RIF) and miscarriage (RM), we analyzed the efficacy and safety of intralipid therapy to obtain a live birth. PATIENTS AND METHODS: Women with unexplained RM and/or RIF were included from 2015 to 2018 from three French university hospitals. RESULTS: Among 187 women treated for unexplained recurrent miscarriages and implantation failures, 26 women with median age of 36 years (29-43) received intralipid therapy. Among these 26 women, 10 women with a median age of 33 years (31-40) had a history of spontaneous recurrent miscarriages, with a median of 5 (4-8) previous miscarriages. Live births occurred in 7 (70 %) pregnancies under intralipids and were significantly more frequent than in women with recurrent miscarriages who did not receive intralipid therapy (n = 20, p = 0.02). Age, number of previous miscarriages, and additional therapies did not significantly differ between the two groups. Among the 26 included women, 16 had a history of recurrent implantation failures, with median age of 37 years (29-43) and median 9.5 (3-19) embryo transfers. Clinical pregnancy occurred in 9 (56 %) women receiving intralipids after embryo transfers under intralipids among which 5 (55 %) resulted in a live birth. Comparing successful pregnancies under intralipids with those with fetal loss, no significant differences have been noted. CONCLUSION: Intralipids could be an effective and safe therapy in women with unexplained recurrent miscarriages and infertility.

Effectiveness of a therapeutic multiple-lifestyle intervention taking into account the periconceptional environment in the management of infertile couples: study design of a randomized controlled trial - the PEPCI study.

BACKGROUND: Infertility is defined as the inability to conceive after 12 months of unprotected intercourse. It affects approximately one in six couples seeking pregnancy in France or western countries. Many lifestyle factors of the couples' pre and peri-conceptional environment (weight, diet, alcohol, tobacco, coffee, drugs, physical activity, stress, sleep…) have been identified as risk factors for infertility in both males and females. The high prevalence rates of unhealthy diets and lifestyles in the reproductive population of industrialized countries are worrisome. Nevertheless, adoption of a healthy lifestyle may improve fertility but lifestyle changes are difficult to achieve and to maintain due notably to behavioral factors. METHODS: Consequently, we decided to propose an interventional study aimed at improving the quality of life of infertile couples before the start of assisted reproductive technology treatment. It is a randomized controlled multicentre trial. Both members of the couples are involved in an integrated global care program (PEPCI for "Parcours Environnement PériConceptionnel en Infertilité") vs. usual care. This global intervention not only considers diet and/or physical activity but follows a holistic approach, including a multidisciplinary assessment to address complete physical, psychological and social well-being. According to patient needs, this includes interventions on weight, exercise, diet, alcohol and drugs, mental and social health. DISCUSSION: The main objective of trial is to demonstrate that periconceptional multidisciplinary care has a positive impact on reproductive functions. We will also focus on feasibility, acceptance, compliance and conditions of success of a multifaceted lifestyle intervention. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov, Identifier: NCT02961907 on November 11, 2016.

Head and neck cancer during pregnancy.

BACKGROUND: The incidence of cancer during pregnancy is low but is slightly increasing. Data on incidence and etiology of head and neck (HN) cancers in pregnant women are rare. We evaluated the frequency, tumor type, associated factors, and specific biomarkers in HN cancers occurring in pregnant (and peripartum) women. METHODS: A systematic literature search was performed on PubMed, for any HN tumor site occurring in pregnant women. RESULTS: Sixty cases of HN cancers occurring during pregnancy were identified. Most of them were oral cavity cancers. Relationships with oncogenic viruses, hormonal disturbance, and shift in maternal immunity profile were identified. CONCLUSION: Carcinogenesis of HN cancers in pregnant women may be led by different cancer type-specific hallmarks. Relevance of these etiological factors with respect to treatments and birth control recommendations is being investigated by the REFCOR in an ambispective study.

Fertility preservation, contraception and menopause hormone therapy in women treated for rare ovarian tumours: guidelines from the French national network dedicated to rare gynaecological cancers.

INTRODUCTION: Rare ovarian tumours include complex borderline ovarian tumours, sex-cord tumours, germ cell tumours and rare epithelial tumours. Indications and modalities of fertility preservation (FP), infertility management, contraindications for hormonal contraception or menopause hormone therapy are frequent issues in clinical practice. A panel of experts from the French national network dedicated to rare gynaecological cancers, and experts in reproductive medicine and gynaecology have built guidelines on FP, contraception and menopause hormone therapy in women treated for ovarian rare tumours. MATERIAL AND METHODS: A panel of 35 experts from different specialties contributed to the preparation of the guidelines, following the DELPHI method (formal consensus method). Statements were drafted after a systematic literature review and then rated through two successive rounds. RESULTS: Thirty-five recommendations were identified, concerning indications for FP, contraindications for ovarian stimulation, contraceptive options and menopause hormone therapy for each tumour type. DISCUSSION: Overall, caution has been recommended in the case of potentially hormone-sensitive tumours such as sex-cord tumours, serous and endometrioid low-grade adenocarcinomas, as well as for high-risk serous borderline ovarian tumours. CONCLUSION: In the context of a scarce literature, a formal consensus method allowed the elaboration of guidelines, which will help clinicians in the management of these patients.

Proportion of Cytotoxic Peripheral Blood Natural Killer Cells and T-Cell Large Granular Lymphocytes in Recurrent Miscarriage and Repeated Implantation Failure: Case-Control Study and Meta-analysis.

We aimed to compare the proportion of peripheral blood natural killer (NK) cells (CD3-CD56+) and T-cell large granular lymphocytes (CD8+CD57+) during preconception in a homogenous group of women with unexplained well-defined recurrent miscarriage (RM) and repeated implantation failure (RIF) vs healthy controls in relation to pregnancy outcomes. This case-control study followed by a literature review and meta-analysis was conducted in three university hospitals. Patients and controls were consecutively recruited from December 2015 to October 2017. In total, 115 women were included in the study: 54 with RM, 41 with RIF and 20 healthy controls with ≥ 2 term births. Percentages of CD3-CD56+ and CD8+CD57+ cells and sub-populations of CD3-CD56+ cells did not differ between cases and controls. The results for women with subsequent miscarriage did not differ from those with live births. The meta-analysis of the literature showed higher NK-cell proportions in RM [mean difference 3.47 (95% CI 2.94-4.00); p < 0.001] and RIF [mean difference 1.64 (95% CI 0.82-2.45); p < 0.001] than controls. However, the heterogeneity between the different studies was high. The proportion of peripheral blood CD3-CD56+ and CD8+CD57+ cells in the preconception period does not reflect the risk of implantation failure or miscarriage and should not be recommended indicators for the management of RM and RIF. Further prospective large studies are needed to develop a reliable peripheral blood marker of immune deregulation.