Efficacy of assisted reproductive technology after ovarian tissue transplantation in a cohort of 11 patients with or without associated infertility factors.

PURPOSE: IVF treatment in women with grafted frozen-thawed ovarian tissue is associated with poor reproductive outcomes. The aim of this study was to evaluate the efficacy of ovarian tissue transplantation (OTT) followed by assisted reproductive technology (ART) in women with or without associated infertility factors. METHODS: This is a prospective cohort study with retrospective data collection including eleven women, four of whom having an infertility factor (IF), who had undergone OTT in one university center between 2005 and 2017, followed by ART in six in vitro fertilization (IVF) centers. RESULTS: In total, 25 of the 85 cycles initiated (29%) were canceled, resulting in 60 oocyte retrievals. Ninety-five oocytes were retrieved: 36 were abnormal or immature, 29/39 fertilized (74%) after ICSI and 13/20 (65%) after IVF. Thirty-five embryos were transferred in seven patients (5/7 patients without IF and 2/4 patients with IF). After ART, one patient with IF experienced two pregnancies, one resulting in a live birth. For all patients, pregnancy rates and live birth rates were 7.4% and 3.7% per embryo transfer, respectively. Nine pregnancies and four live births occurred after spontaneous conception in five patients without IF, none in the infertility group. CONCLUSION: This study confirms that IVF treatment in women with grafted frozen-thawed ovarian tissue is associated with poor outcomes. However, the chances of natural conception are high in women without IF. Patients with IF, without the possibility of spontaneous pregnancy, should be informed of poor reproductive outcomes after OTT followed by ART. TRIAL REGISTRATION NUMBER: NCT02184806.

Invasive and in situ cervical cancer associated with pregnancy: analysis from the French cancer network (CALG: Cancer Associé à La Grossesse).

PURPOSE: To describe the oncologic and obstetric outcomes of patients diagnosed with invasive cervical cancer (ICC) and in situ adenocarcinoma (ISA) during pregnancy or during the year following delivery. METHODS: This retrospective observational study involved a cohort of 28 patients diagnosed with invasive cervical cancer (20 patients) or in situ adenocarcinoma (eight patients) during pregnancy or during the year following delivery who received expert opinion from physicians of the Cancer Associé à La Grossesse (CALG) network between 2005 and 2018. Descriptive results were expressed in median, range and interquartile range (IQR). RESULTS: Between 2005 and 2018, 20 patients with ICC and eight with ISA received expert opinion from physicians of the CALG network. Both ICC and ISA were mostly diagnosed during pregnancy with a median term at diagnosis of 23.3 weeks of gestation (WG) for ICC and 7.3 WG for ISA. Overall, the median age at diagnosis for both ICC and ISA was 33 years. Most ICCs (n = 9) had FIGO stage ≥ IB2 and five underwent neoadjuvant chemotherapy at a median term of 22.5 WG. Seventeen patients with ICC underwent surgery. Three patients had medical termination of the pregnancy. Two patients experienced recurrence and three died. Median time of follow-up was 59.3 months (IQR 30.5-129.2). CONCLUSION: Management of cervical cancer during pregnancy is challenging especially in terms of maternal outcomes with a relative poor prognosis requiring a multidisciplinary expert advice.

[Expert centre Cancer du sein et Grossesse (CALG): Concordance between the proposed therapeutics and those finally received]. / Centre expert Cancer du sein et Grossesse (CALG) : concordance entre la proposition du CALG et la prise en charge effective.

OBJECTIVE: Breast cancer associated with pregnancy (CSAG) is a rare condition whose management justifies the use of expert center. The Pregnancy-Associated Cancer Network (CALG) was created in France to optimize therapeutic management. The objective of our study was to evaluate its impact on the therapeutic management of CSAGs and the discrepancy rate between the CALG proposal and the treatment performed. METHOD: A retrospective study including 58 CSAGs for which the opinion of the CALG network was solicited between January 2015 and November 2017. A questionnaire was addressed to the practitioner requesting the network. These practitioners were contacted to know the treatments received by the patient to assess the discrepancy rate. RESULTS: In 70% of the cases, the CALG network was solicited before any therapeutic treatment. When the opinion was requested after initiation of therapy, the discrepancy rate between the CALG proposal and the one practiced was 47%. Of the 46 physicians contacted, the response rate was 62.5% (30/46). In 90% of cases, the therapy proposed by the CALG network was the one received by the patient. CONCLUSION: This study emphasizes the need to refer to an expert center before treatment of a CSAG and the need for the contribution of doctors requesting the expert center to inform them of the follow-up of patients and children.

Pregnancy outcomes after controlled ovarian hyperstimulation in women with endometriosis-associated infertility: GnRH-agonist versus GnRH-antagonist.

BACKGROUND OR OBJECTIVE: Endometriosis is common in women referred for infertility. In vitro fertilization provides good results but the choice of the best-controlled ovarian hyperstimulation protocol remains a subject of debate. The objective of this retrospective study was to compare pregnancy outcomes in women with endometriosis-associated infertility after COH with a long agonist protocol or a six-week oral contraception-antagonist protocol. MATERIAL AND METHODS: Retrospective analysis of a prospective database identified 284 COH cycles - 165 with GnRH-agonist protocol (GnRH-agonist group) and 119 with GnRH-antagonist protocol (GnRH-antagonist group) - in 218 women, with endometriosis from January 2013 to October 2015. RESULTS: No difference in the epidemiological characteristics was found between the groups. Per started cycle, pregnancy and live-birth rates after fresh embryo transfer were higher with the GnRH-agonist protocol (25% vs. 13%, P=0.02 and 18% vs. 8%, P=0.04, respectively). Considering analysis per cycle with embryo transfer, the pregnancy rate was similar in both groups while the live-birth rate was higher in the GnRH-agonist group (29% vs. 17%, P=0.053 and 22% vs. 10%, P=0.02, respectively). No difference was observed between the groups with freeze-thaw embryo transfer. Subgroup analysis (endometrioma alone, deep infiltrating endometriosis with and without endometrioma, endometriosis with and without adenomyosis) revealed no difference between the groups for either pregnancy or live-birth rates. CONCLUSION: A GnRH-agonist protocol appears to result in higher pregnancy and live-birth rates after fresh embryo transfer in women with endometriosis-associated infertility, suggesting that a GnRH-antagonist protocol might negatively impact endometrial receptivity.

[Viral failure in infants perinatally infected with HIV: A double punishment]. / Échec virologique chez les nourrissons infectés par le VIH par transmission périnatale : une double peine.

BACKGROUND: Considering the remarkable efficacy of the strategies for preventing mother-to-child transmission of HIV infection (PMTCT), failures are rare in high-resource countries and deserve further investigation. Moreover, infants have been found to be at increased risk of viral failure. We analyzed the factors related to the children's environment, including maternal psychological factors that may be associated with viral failure in children diagnosed before the age of 1 year. PATIENTS AND METHODS: Retrospective study of all HIV-infected infants, born in France between July 2003 and July 2013, diagnosed before the age of 1 year, cared for in a single reference center, comparing the group of children in viral success to the group of children presenting at least one episode of viral failure, using data available in their medical, psychological and social files. RESULTS: Out of 1061 infants included in the prospective PMTCT follow-up, eight infants were found HIV-positive and an additional six cases were referred from other centers before the age of 1 year, for a total of 14 children born to 13 mothers. Seven children presented durable optimal viral control (VL<50 c/mL) whereas seven others did not reach or maintain optimal viral control over time. The main difference between the two groups was the presence among the mothers of children with viral failure of severe psychological disorders, leading to treatment adherence problems in the mothers who were aware of their HIV status before pregnancy, and difficulties in giving their children's treatments correctly. CONCLUSIONS: Although seroconversion during pregnancy is responsible for a significant proportion of residual transmission in high-resource countries, severe psychological or psychiatric conditions in HIV-positive mothers play an important role on the risk of both MTC residual transmission and viral failure in their infants.

[Deep infiltrative endometriosis without digestive involvement, what is the impact of surgery on in vitro fertilization outcomes? A retrospective study]. / La résection de l'endométriose profonde sans atteinte digestive améliore-t-elle les résultats de la fécondation in vitro ? Une étude retrospective.

OBJECTIVES: To evaluate the impact of complete removal of endometriosis in case of deep infiltrative endometriosis without digestive involvement, on in vitro fertilization outcomes. METHODS: Retrospective monocentric study. We included infertile women with deep infiltrative endometriosis without colorectal involvement that underwent IVF. Women were divided in two groups, following their history: "surgery" when they underwent complete endometriosis resection before IVF and "without surgery" when they underwent IVF without endometriosis removal. We analysed IVF outcomes considering pregnancy rates per cycle and cumulative pregnancy rates per patient. RESULTS: We included 72 patients: 35 in the "surgery" group and 37 in the "without surgery" group. Women in the two groups were comparable in terms of baseline characteristics (age, body mass index, anti-Müllerian hormone, antral follicular count), endometriosis localizations and in vitro fertilization parameters. Cumulative pregnancy rates per patient were similar in both groups (40 % in the "surgery" group and 41 % in the "without surgery" group; P=1). Clinical pregnancy rate per cycle were also comparable groups (24 % in the "surgery" group and 28 % in the "without surgery" group; P=0.67). Surgery performed was comparable in women that became pregnant and in women that did not. Age was lower in women that became pregnant (P=0.01) and there were more pregnancy obtained in women under 35 years. CONCLUSION: In women with deep infiltrative endometriosis without digestive involvement, in vitro fertilization outcomes were not impacted by surgery. Therapeutic choice between IVF or surgery as first-line treatment remains thus questionable and shall be guided by other influencing factors, such as pain symptomatology, age, tubal permeability, ovarian reserve, partner's sperm characteristics and woman's choice.

Pregnancy-associated breast cancer is as chemosensitive as non-pregnancy-associated breast cancer in the neoadjuvant setting.

BACKGROUND: The aim of this study was to determine the chemosensitivity of pregnancy-associated breast cancer (PABC) in the neoadjuvant setting by comparing the observed pathological complete response (pCR) rate with the rate predicted by a validated nomogram. METHODS: Data from 48 PABC patients who received neoadjuvant chemotherapy (NACT) were collected. To predict the response rate to chemotherapy, we used well-calibrated logistic regression-based nomograms to calculate individual probability of pCR. RESULTS: Observed rates of pCR were concordant with predictions in the whole sample and in the analyzed subgroups. For the whole sample, the area under the receiver-operated curve (AUC) was 0.77 (95% CI 0.66-0.87). The calibration of predicted and observed probabilities was excellent. In the subgroup analyses (NACT initiated during pregnancy or postpartum, NACT with only anthracycline or both anthracycline and taxanes), discriminations assessed by AUC were significantly above 0.5, except for patients treated with anthracycline only. The interpretation was limited by a lack of power. CONCLUSION: Through the use of nomograms, our study demonstrates that PABC is as chemosensitive as non-PABC and suggests that taxanes should be part of the NACT regimen for PABC. Further studies are warranted to increase the power of the presented data.

Abnormal Sylvian fissure on prenatal cerebral imaging: significance and correlation with neuropathological and postnatal data.

OBJECTIVE: To illustrate and determine the significance of abnormal Sylvian fissure development (or abnormal operculization) in cases in which prenatal cerebral imaging is suggestive of underlying cortical dysplasia. METHODS: This was a retrospective study of 15 fetuses at 24-34 weeks in which abnormal operculization was identified on prenatal cerebral imaging and for which follow-up data were available. The imaging findings were correlated to macro- and microscopic neuropathological data (n = 11) or to postnatal clinical and imaging findings (n = 4). RESULTS: On microscopic examination of fetuses from 11 terminated pregnancies, abnormal operculization was associated with cortical dysplasia in four cases and the cortex was normal in seven. Abnormal operculization was associated with cortical dysplasia in only one of the four liveborn infants. Cases of abnormal Sylvian fissure development with normal cortical architecture were classified, according to associated anomalies of the central nervous system, into one of five groups: those with neural tube defects, microcephaly or frontal hypoplasia, glutaric aciduria, other cerebral abnormalities, and extracerebral anomalies. CONCLUSION: Abnormal operculization on prenatal imaging does not systematically reflect underlying cortical dysplasia. It may be related to extracortical factors such as abnormal cerebral volume or other developmental anomalies of the central nervous system. An understanding of the significance of abnormal Sylvian fissure development could be useful in integrating its analysis into a more general one of the whole central nervous system.

[Precancerous cervical lesions during pregnancy: diagnostic and treatment]. / Diagnostic et prise en charge des lésions précancéreuses du col utérin pendant la grossesse.

The rate of CIN discovered during pregnancy is around 1%. Pregnancy should be a period for the checking of pap-smear. So a pap-smear should be performed if the last one is more than two years old. If the pap-smear is less than two years old, a copy of its result should be obtained. The cervical cytology is valid during pregnancy, and usually pregnancy induced an opening of the junction zone that helps to have a good evaluation of the cervix. When atypical cells are found in the pap-smear performed during pregnancy, the management should include a colposcopy and biopsies, whatever the severity of the abnormal cells (ASC-US, ASC-H, AGC, LBG, LHG, invasive carcinoma). The biopsy should be guided by the colposcopy. Biopsy is required for an optimal diagnosis. The management of the pregnant patient should be based on the results of cytology, and colposcopy and biopsies. Currently there is no indication for HPV-typing during pregnancy. If an invasive tumor is excluded after cytology, and colposcopy and biopsy, no treatment is performed during pregnancy, and the treatment is postponed after delivery following a complete cervical reevaluation. If an invasion cannot be excluded with the biopsy; a diagnostic conization completed with a cerclage should be performed. This procedure should be exceptionally performed. During pregnancy, CIN lesions are usually stable or regress; progression of CIN is rare. When managing an abnormal pap-smear during pregnancy, a microinvasive cervical cancer may be found on a biopsy or conization specimen. Staging of these lesions requires always a conization and eventually a pelvic MRI. Microinvasive cervical cancers can be only followed until the end of the pregnancy.