Impact of a positive Chlamydia trachomatis serology on cumulative IVF live birth rate.

RESEARCH QUESTION: Does positive Chlamydia trachomatis serology have an impact on the cumulative live birth rate from IVF? DESIGN: A retrospective matched cohort study compared women with positive Chlamydia trachomatis serology (group A) who underwent IVF treatment between January 2016 and December 2021 with a control group of women with negative Chlamydia trachomatis serology (group B). The main outcome measures were the cumulative live birth rate per IVF cycle and the live birth rate per embryo transfer. Secondary outcomes were the cumulative rates of clinical pregnancy, ectopic pregnancy and pregnancy loss calculated per IVF cycle and per embryo transfer. RESULTS: A total of 151 women in group A were matched 1:2 to 302 women in group B, representing 220 and 440 IVF cycles, respectively. Women with a history of Chlamydia trachomatis infection had a significantly higher rate of tubal obstruction (P < 0.001), excluded or operated hydrosalpinx (P = 0.002) and/or history of chronic endometritis (P < 0.001). There were no statistically significant differences between the two groups in the mean number of mature oocytes retrieved, fertilization rate or implantation rate. The IVF cumulative live birth rate per cycle was similar in the two groups (36.7% in group A versus 34.9% in group B, P = 0.692). The cumulative rates of clinical pregnancy, pregnancy loss, biochemical pregnancy and ectopic pregnancy were comparable between the two groups. CONCLUSION: Positive Chlamydia trachomatis serology has no impact on IVF pregnancy outcomes.

Impact of moderate-to-severe endometriosis on IVF cumulative live birth rate: a retrospective matched cohort study.

RESEARCH QUESTION: Does moderate-to-severe endometriosis have an impact on cumulative live birth rates (cLBR) and IVF outcomes? DESIGN: In this retrospective matched cohort study, women with moderate-to-severe endometriosis undergoing IVF or intracytoplasmic sperm injection treatment from January 2015 to December 2020 were matched 1:2 to women with other causes of infertility (control group). The main outcome was cLBR per cycle and per woman, and secondary outcomes were number of oocytes retrieved and number of mature oocytes, fertilization rate, total number of embryos and usable embryos, implantation rate, clinical pregnancy rate and miscarriage rate per cycle. RESULTS: In total, 195 women with endometriosis were matched with 390 women without endometriosis (323 and 646 cycles, respectively). Women with endometriosis had significantly fewer oocytes retrieved than women in the control group (P=0.003) despite higher doses of gonadotropins, but had a similar number of mature oocytes, fertilization rate, and total number of embryos and usable embryos. cLBR per cycle and per women did not differ significantly between the endometriosis group and the control group (19.8% versus 24.3%, P = 0.12; 32.3% versus 37.2%, P = 0.24, respectively). In women with endometrioma, a history of cystectomy did not impact cLBR per cycle (28.3% versus 31.9%, P = 0.68). We did not observe any significant impact of tobacco use in the endometriosis group compared with the control group (16.4% versus 25.9%, P = 0.13). CONCLUSION: This matched cohort study did not observe a significant impact of moderate-to-severe endometriosis on cLBR among women undergoing IVF. These data are reassuring for the counselling of infertile women with endometriosis before IVF.

Knowledge, professional attitudes, and training among health professionals regarding male contraceptive methods.

OBJECTIVES: Health professionals are at the forefront of information and acceptability regarding contraceptive methods, however only one study evaluated their knowledge of male contraception (MC) including hormonal MC (HMC) and thermal MC (TMC). Our objective was to evaluate the knowledge, professional attitudes, and training of French practitioners regarding the management of couple contraception by male contraception (MC). STUDY DESIGN: We designed a descriptive, cross-sectional, multicentre study in 2,396 French practitioners belonging to national or regional institutions involved in contraception. We solicited practitioners by e-mail to complete an anonymous questionnaire; we analysed their knowledge, professional attitudes, and training regarding the management of couple contraception by MC. RESULTS: The overall participation rate was 18% (427/2,396). Condoms, withdrawal, and vasectomy were known by 98%, 89%, and 76% of the population, respectively. Hormonal MC and Thermal (TMC) were known by 10% and 24% of the population, respectively. Fifty-five percent of the population never or infrequently offered MC during a couple's contraceptive request consultation. Only 14% of the population had ever participated in training on MC; 96% wanted to be better trained on MC, and 87% expressed a willingness to participate in training on the subject. CONCLUSIONS: Health professionals involved in contraception have unsatisfactory knowledge about MC methods based on spermatogenesis inhibition and are eager to have more information about them. To advance the acceptability and dissemination of MC methods, it seems imperative to enhance research in the field and to provide health professionals with an adapted training programme.

Domestic use of pesticides during early periods of development and risk of testicular germ cell tumors in adulthood: a French nationwide case-control study.

BACKGROUND: Testicular germ cell tumours (TGCT) are the most frequent cancers in young men in developed countries and their incidence rate has doubled worldwide over the past 40 years. Early life exposures to pesticides are suspected to increase TGCT risk. Our research aimed at estimating adult TGCT risk associated with parental domestic use of pesticides during early periods of child development. METHODS: We conducted a case-control study of 304 TGCT cases, aged 18-45 years old, recruited in 20 French university hospitals, and 274 controls frequency-matched on hospital and birth year. Participants' mothers provided information on their domestic use of pesticides from 1 year before start of pregnancy to 1 year after their son's birth, for gardening activities, treatment of indoor plants, pets, wood and mold, and pest control. Odds ratios (OR) for TGCT (overall and by histological subtype) and 95% confidence intervals (CI) were estimated using conditional logistic regression. RESULTS: Prevalence of reported domestic use of pesticides was 77.3% for insecticides, 15.9% for fungicides and 12.1% for herbicides. While no association was found for any use of insecticides (OR = 1.27, CI = 0.80-2.01) or herbicides (OR = 1.15, CI = 0.67-2.00), elevated risks of TGCT overall (OR = 1.73, CI = 1.04-2.87) and non-seminoma subtype (OR = 2.44, CI = 1.26-4.74) were observed for any use of fungicides. When specific purposes were examined, using fungicides and/or insecticides for woodwork (OR = 2.35, CI = 1.06-5.20) and using insecticides on cats and dogs (OR = 1.95, CI = 1.12-3.40) were associated with increased risk of non-seminoma subtype. We found no association for seminoma subtype. CONCLUSIONS: Although recall bias may partially explain the elevated ORs, our study provides some evidence of a positive association between domestic use of pesticides during early periods of development, particularly fungicides and risk of adult TGCT and non-seminoma. Given the common domestic use of pesticides in France, further research on TGCT risk is warranted.

Nomograms for predicting adverse obstetric outcome in IVF pregnancy: A preliminary study.

BACKGROUND: In a previous study, we showed that the obstetric complication rate after in vitro fertilization (IVF) pregnancy was 40%. The main objective of our study was to determine maternal prognosis factors that influence the IVF pregnancy outcome. METHODS: We conducted an observational retrospective monocentric study between January 2014 and January 2018. Pregnancy over 22 gestational weeks (GW) obtained after IVF in our infertility clinic was included. Maternal characteristics and pregnancy outcome were collected. RESULTS: Data from 498 IVF pregnancies were analyzed. The most significant maternal prognosis factors for obstetric complications were maternal age above 40 years (OR 3,0 [95% IC 1,30-7,09], P = 0,010), twin pregnancies (3.8 [95% IC 1.49-9.99], P = .005), daily maternal smoking above 10 cigarettes (7.1 [95% IC 1.22-41.74], P = .029), maternal obesity (2.2 [95% IC 1.19-4.07], P = .012), endometriosis stages III and IV (6.4 [95% IC 1.52-27.04], P = .011), and history of ovarian hyperstimulation syndrome (OHSS) in early pregnancy (5.7 [95% IC 1.29-24.74], P = .021). Risk increase was independent of pregnancy type (singleton or twin) and allowed the elaboration of 2 nomograms. CONCLUSIONS: Our study showed a link between some maternal factors and increase in obstetric complications after IVF. Screening of these factors during preconceptional visit is essential to identify at high-risk pregnancies and adapt their monitoring.

Influence of polycyclic aromatic hydrocarbon exposure on IVF: now is the time to focus on women.

RESEARCH QUESTION: Is polycyclic aromatic hydrocarbon (PAH) exposure associated with the reproductive outcomes of IVF treatment? DESIGN: A prospective, small-scale monocentric cohort study of couples who underwent IVF treatment between January 2018 and June 2019. Both members of each couple answered a questionnaire on PAH exposure and provided urine samples to measure urinary 1-hydroxypyrene (1-OHP) the day before oocyte retrieval and semen collection for fertilization. To assess the specific PAH exposure of gamete cells, immunostaining was conducted on both spermatozoa and granulosa cells obtained during IVF with an anti-benzo(a)pyrene diol epoxide (BPDE) monoclonal antibody that recognizes BDPE-DNA adducts. To assess DNA damage, a comet assay on spermatozoa was conducted. The PAH exposure was compared between couples who had positive HCG and couples who had negative HCG on day 14 after embryo transfer. RESULTS: Eighteen couples were included. The mean 1-OHP level in women whose HCG tests were positive (n = 6) was significantly lower than that in women with negative HCG tests (0.098 [0.042-0.170] versus 0.177 [0.067-0.812] µg/g creatinine; P = 0.048). The presence of BPDE-DNA adducts in granulosa cells of women with a negative (29.7 [16.2-57.5] arbitrary units) or positive HCG test (20.3 [9.3-23.3] arbitrary units) were not significantly different (P = 0.092). The urinary 1-OHP levels of men and BPDE-DNA adducts in spermatozoa showed no differences between groups. CONCLUSIONS: This exploratory research should encourage further studies to determine the effect of women's exposure to PAHs on reproductive outcomes of IVF treatment.

[Cryoconservation of gametes: how to perform?] / Conservation des gamètes : quelles modalités ?

Cryoconservation of gametes : how to perform ? The patients can preserve their gametes when they are exposed to potential gonadotoxic pathology or treatment. In this context, the French bioethical law clearly states the obligation to inform the patients about the risks for their fertility and the possibilities to cryopreserve their gametes. Regional platforms of fertility preservation allow notably for the coordination of the oncology teams and the CECOS. For the men, sperm freezing is achieved by a slow and controlled temperature protocol. For the women, the oocytes are usually vitrified after hormonal stimulation and ovarian punction. For both, the gametes are cryopreserved in straws and stored in liquid nitrogen until use in assisted reproductive treatment (ART). Each year, the CECOS keeping the gametes interrogates patients on their wish to continue, or not, the cryoconservation. The gametes can only be used in ART by the patients only during their lifetime and with their consent, without alterations related to the duration of storage.

Conservation des gamètes : quelles modalités ? Les patient(e)s peuvent conserver leurs gamètes lorsqu'ils( ou elles) sont exposé(e)s à une pathologie ou un traitement potentiellement gonadotoxique. Dans ce contexte, la loi de bioéthique énonce très clairement l'obligation d'informer les patients des risques pour leur fertilité et des possibilités de conservation de leurs gamètes. Les plateformes régionales de préservation de la fertilité assurent la coordination entre les équipes d'oncologie et les centres d'étude et de conservation des oeufs et du sperme humains (CECOS) pour la mise en oeuvre de cette préservation. Pour les hommes, la congélation des spermatozoïdes est réalisée par une descente en température lente et contrôlée. Pour les femmes, la cryoconservation des ovocytes se fait par vitrification après stimulation hormonale et ponction ovarienne. Dans les deux cas, les gamètes sont conservés dans des paillettes qui sont stockées dans une cuve d'azote liquide jusqu'à utilisation en assistance médicale à la procréation (AMP). Le CECOS conservant les gamètes interroge chaque année par courrier les patients concernés sur leur souhait de poursuivre, ou non, la cryoconservation. Les gamètes pourront être utilisés en AMP par les patients de leur vivant et après leur consentement, sans altération liée à la durée de stockage.

Factors associated with a poor prognosis for the IVF-ICSI live birth rate in women with rAFS stage III and IV endometriosis.

PURPOSE: To assess the factors associated with a poor prognosis for a cumulative IVF live birth rate (LBR) in women with stage III and IV endometriosis according to the revised classification of the American Fertility Society (rAFS). METHODS: A retrospective cohort study was conducted between January 1, 2010, and December 31, 2014, in our Reproductive Medicine Center. We analyzed different factors associated with a poor prognosis for a cumulative IVF LBR in women with rAFS stage III and IV endometriosis. A total of 101 patients were included, representing 232 IVF-ICSI cycles and 212 embryo transfers. The primary endpoint was the cumulative LBR per cycle and per patient. RESULTS: The cumulative LBR per cycle was 14.7% (n = 34) and that per patient was 31.7% (n = 32). The cumulative LBR was significantly decreased by active smoking [adjOR = 3.4, 95% CI (1.12-10.60), p = 0.031], poor ovarian response (POR) according to the Bologna criteria [adjOR = 11.5, 95% CI (1.37-96.83), p = 0.024], and rAFS stage IV [adjOR = 3.2, 95% CI (1.13-8.95), p = 0.024]. The cumulative LBR per women was 59.4% without factors associated with a poor prognosis and 25.6% in the case of one factor, and it decreased to 7.7% in the case of two or three factors (p < 0.001). CONCLUSION: Active smoking, POR according to the Bologna criteria, and rAFS stage IV endometriosis had a negative impact on the IVF-ICSI cumulative LBR for women with rAFS stage III and IV endometriosis. Because smoking dramatically decreases the LBR with endometriosis, stopping smoking before IVF-ICSI should be strongly advised.

IVF oocyte retrieval: prospective evaluation of the type of anesthesia on live birth rate, pain, and patient satisfaction.

PURPOSE: Does the type of anesthesia (paracervical block (PCB) or general anesthesia (GA)) impact live birth rate, pain, and patient satisfaction? METHODS: A non-randomized prospective cohort study was conducted in women treated for IVF. Two groups of patients were prospectively included: the PCB group (n = 234) and the GA group (n = 247). The type of anesthesia was determined by the patients. The primary endpoint was cumulative live birth rate by OR. Secondary endpoints were self-assessment of the patients' peri-operative abdominal and vaginal pain vs the doctors' evaluations during PCB, post-operative abdominal and vaginal pain level, and patient satisfaction in both groups. Pain levels were assessed with a numerical rating scale (NRS). RESULTS: The live birth rate was similar in both groups (19.8% in the GA group vs 20.9% in the PCB group, P = 0.764). During oocyte retrieval in the PCB group, the physicians significantly under-estimated the vaginal pain experienced by the patients (3.04 ± 0.173 for patients vs 2.59 ± 0.113 for surgeons, P = 0.014). Post-operative vaginal and abdominal pain were significantly greater in the PCB group compared to the GA group (2.26 ± 0.159 vs 1.66 ± 0.123, respectively, P = 0.005, and 3.80 ± 0.165 vs 3.00 ± 0.148, respectively, P < 0.001). Patients were more significantly satisfied with GA than with PBC (P < 0.001). CONCLUSION: Because the LBR was similar in both groups and patient satisfaction was high, the choice of anesthesia should be decided by the patients.

Successful IVF pregnancy despite inadequate ovarian steroidogenesis due to congenital lipoid adrenal hyperplasia (CLAH): a case report.

Steroidogenic acute regulatory protein (StAR) mutations are the most frequent aetiologies of congenital lipoid adrenal hyperplasia (CLAH). Phenotypes may vary, and puberty may be absent in affected individuals. To date, only two pregnancies have been described in 46,XX CLAH patients with StAR mutations; these patients exhibited ovarian steroidogenesis along with spontaneous puberty and menarche and normal menses. The patient described here presented with CLAH caused by the homozygous (unreported, 1 bp) deletion c.719del in the StAR gene, which was diagnosed after acute adrenal insufficiency when the patient was 10 days old. The patient did not undergo spontaneous puberty, so puberty was induced by HRT when the patient was 13 years old. At the age of 25 years, the patient was referred to our reproductive unit because she desired to conceive. An initial cycle of clomiphene, stimulation produced follicular growth with two mature follicles measuring 18 and 15 mm, respectively, but the plasma oestradiol levels remained low (18 pg/ml) and the endometrium was thin (3 mm). Pregnancy was finally achieved after ovarian stimulation, IVF and transfer of frozen-thawed embryos after endometrial preparation with HRT. A normal female child was delivered following a 40 weeks' uneventful pregnancy. We therefore report the first IVF pregnancy achieved in a 46,XX CLAH patient homozygous for a StAR mutation, with inadequate ovarian steroidogenesis and no spontaneous puberty.

Surgical diminished ovarian reserve after endometrioma cystectomy versus idiopathic DOR: comparison of in vitro fertilization outcome.

STUDY QUESTION: Does the live birth rate after IVF depend on the etiology of diminished ovarian reserve (DOR)? SUMMARY ANSWER: IVF outcome and live birth rate are significantly impaired in women with DOR caused by a previous cystectomy for endometrioma compared with women with idiopathic DOR. WHAT IS KNOWN ALREADY: The safety of the surgical treatment of endometriomas is being discussed in terms of damage to ovarian reserve. Several studies have reported a poor response to controlled ovarian stimulation and a significantly impaired IVF outcome in women with DOR consecutive to an endometrioma cystectomy compared with women with tubal factor infertility. STUDY DESIGN, SIZE, DURATION: Retrospective case-control study conducted in women aged under 40 treated in our Reproductive Medicine Center between January 2010 and January 2014 for a DOR defined by anti-Müllerian hormone level <2 ng/ml. Two groups of patients were selected: group A included patients with a DOR diagnosed after cystectomy(s) for endometrioma(s), group B included patients with an idiopathic DOR. In each group, subgroups of patients 'poor ovarian responders', based on the ESHRE criteria ('Bologna criteria'), have been established. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 51 patients in group A were matched to 116 patients in group B, representing respectively 125 and 243 IVF cycles. Among them, 39 patients in group A and 78 patients in group B validated strictly by the Bologna criteria, representing 99 and 189 IVF cycles, respectively. Each patient underwent a controlled ovarian hyperstimulation and IVF with fresh embryo transfer. Primary end-point was the live birth rate. Secondary end-points were the number of retrieved oocytes, fertilization rate, implantation rate, clinical pregnancy rate, spontaneous abortion rate and cycle cancelation rate. MAIN RESULTS AND THE ROLE OF CHANCE: Significantly lower pregnancy (11.2% in group A versus 20.6% in group B, P = 0.02) and live birth (7.2 versus 16.9% respectively, P = 0.01) rates per cycle were assessed in women in group A compared with women in group B. The same results were obtained in the Bologna criteria subgroup analysis with a significantly lower pregnancy (9.1 versus 20.1%, P = 0.016) and live birth (5.1 versus 15.3%, P = 0.001) rates per cycle in women in subgroup A compared with women in subgroup B. Patients in group A required significantly higher gonadotrophins doses (2881 IU ± 1111 versus 2526 IU ± 795, P = 0.005), longer ovarian stimulation (10.6 Days ± 2.8 versus 9.9 Days ± 2.4, P = 0.019) and higher cancelation rate for poor response (12 versus 6.2%, P = 0.05). Despite a mean number of retrieved oocytes similar with the group B (5.4 ± 3.1 and 5.1 ± 3.2, NS), and a significantly higher fertilization rate (65.7 versus 47.2%, P < 0.001), women in group A showed a significantly lower implantation rate (7.2 versus 13.5%, P = 0.03). Abortion rate, ectopic pregnancy rate and multiple pregnancy rate were similar in both groups. LIMITATIONS, REASONS FOR CAUTION: Data were collected retrospectively using the database of our Department. Sample size is relatively small but our study provides statistically significant evidence that the chances of IVF success are decreased in women with DOR after cystectomy for endometrioma. Further larger series are needed to confirm these findings. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge, this is the first study evaluating IVF outcome in patients with DOR after cystectomy(s) for endometrioma(s) versus in patients with an idiopathic DOR. In addition to the risk of damaging ovarian reserve, we hypothesize that endometrioma surgery would not have qualitative benefits on results in IVF in patients with DOR. STUDY FUNDING/COMPETING INTERESTS: The authors have no competing interests to declare.

Real-life users of hormonal or thermal male contraception: An analysis of female partners' motivation, experience, and satisfaction.

BACKGROUND: Two male contraceptive methods that inhibit spermatogenesis currently exist: thermal male contraception and hormonal male contraception. Only five studies have been conducted on the acceptability of these methods among men; among women, only the hypothetical acceptability of such a male contraceptive approach as the sole contraception method used by a couple has been evaluated. OBJECTIVES: To evaluate the motivation, experience, and satisfaction of female partners in couples using hormonal male contraception or thermal male contraception as the sole contraception. MATERIALS AND METHODS: In this cross-sectional study, 123 male users of hormonal male contraception or thermal male contraception as the couple's sole contraception method were asked to invite their female partner to participate in an anonymous online survey. The questionnaire included 95 questions exploring population characteristics, contraceptive and pregnancy history, motivations for choosing hormonal male contraception or thermal male contraception, the experience of the women in the successive phase of use, relationships with their partner, and satisfaction with the contraception method. RESULTS: The response rate among participating women was 69% (59/86). The two main reasons for choosing male contraceptive were the desire to share the contraception role in the couple (65%) and the desire of the man to take charge of the contraception (61%). The sexual satisfaction score increased significantly between the contraceptive methods used before hormonal male contraception or thermal male contraception and the phase of contraceptive use (p < 0.01). The overall satisfaction level with thermal male contraception or hormonal male contraception was rated at 3.7 ± 0.6 out of 4. Women mostly recommended hormonal male contraception or thermal male contraception because of the share of contraceptive responsibility and mental load (n = 23/54, 43%). DISCUSSION: This population of women seemed to have struggled to find a contraceptive method that suited them, but most took advantage of thermal male contraception or hormonal male contraception and trusted their male partner to take charge of contraception use. CONCLUSION: The positive evaluation from women in partnerships using thermal male contraception and hormonal male contraception should encourage the development of these methods.

Ultrastructural interactions and genotoxicity assay of cerium dioxide nanoparticles on mouse oocytes.

Cerium dioxide nanoparticles (C(e)O2 ENPs) are on the priority list of nanomaterials requiring evaluation. We performed in vitro assays on mature mouse oocytes incubated with C(e)O2 ENPs to study (1) physicochemical biotransformation of ENPs in culture medium; (2) ultrastructural interactions with follicular cells and oocytes using Transmission Electron Microscopy (TEM); (3) genotoxicity of C(e)O2 ENPs on follicular cells and oocytes using a comet assay. DNA damage was quantified as Olive Tail Moment. We show that ENPs aggregated, but their crystal structure remained stable in culture medium. TEM showed endocytosis of C(e)O2 ENP aggregates in follicular cells. In oocytes, C(e)O2 ENP aggregates were only observed around the zona pellucida (ZP). The comet assay revealed significant DNA damage in follicular cells. In oocytes, the comet assay showed a dose-related increase in DNA damage and a significant increase only at the highest concentrations. DNA damage decreased significantly both in follicular cells and in oocytes when an anti-oxidant agent was added in the culture medium. We hypothesise that at low concentrations of C(e)O2 ENPs oocytes could be protected against indirect oxidative stress due to a double defence system composed of follicular cells and ZP.

Feasibility and efficiency of delayed ovarian stimulation and metaphase II oocyte banking for fertility preservation and childbearing desire after fertility-impairing treatment.

The aim of our study was to evaluate the feasibility and efficiency of delayed ovarian stimulation and metaphase II oocyte banking for fertility preservation after fertility-impairing treatment regardless of the initial disease. We conducted a cohort study based on population of women < 40 years of age with diminished ovarian reserve caused by fertility-impairing treatment (n = 129). Three groups of women were compared according to the type of initial disease: hematological malignancies, solid tumors, and benign diseases. The primary endpoint was the number of metaphase II oocytes collected per woman. We studied the cumulative live-birth rate per cycle with fertilized metaphase II oocyte, for women who wanted to conceive. We studied 245 delayed controlled ovarian stimulation cycles in 129 women: 201 for fertility preservation and 44 for in vitro fertilization and fresh embryo transfers. The number of metaphase II oocytes collected per woman after banking was similar in the three groups, with a mean of 10.7 ± 4.6, 12.3 ± 9.1, and 10.1 ± 7.6 metaphase II oocytes (p = 0.46), respectively. In the subgroup of women who wanted to conceive, the cumulative live birth rate per woman was 38%, with 8 live births for these 21 women. After fertility-impairing treatment, practitioners should discuss a fertility preservation procedure for banking metaphase II oocytes.

Efficient pathway for men fertility preservation in testicular cancer or lymphoma: a cross-sectional study of national 2018 data.

BACKGROUND: In 15-49 years-old men, the main cancers are testicular cancer (TC) and lymphomas (L): freezing of ejaculated sperm is primarily used for male fertility preservation (FP) before cancer treatment. Our objective was to analyze the French FP rate in 15-49 years-old men diagnosed with TC or L in 2018. We designed a national descriptive cross-sectional study of sperm banking rate in men with a diagnosis of TC, Hodgkin L (HL) or non-Hodgkin L (NHL). From the French National Cancer Institute (INCa) 2018 data, we extracted the estimated incidence of TC and L in metropolitan France. From the 2018 activity report of CECOS network (Centers for Study and Banking of Eggs and Sperm), we extracted the number of men with TC or L who banked ejaculated sperm. We estimated the proportion of 15-49 years-old men diagnosed with TC or L who banked sperm. RESULTS: Among 15-49 years-old men, INCa estimated 38,048 new cancer diagnoses in metropolitan France in 2018: 2,630 TC and 3,913 L (943 HL and 2,970 NHL). The CECOS network provided data from 26/27 metropolitan centers (96% response rate): 1,079 sperm banking for men with TC, 375 for HL and 211 for NHL. We estimated that the 2018 sperm banking rate in France was 41% for TC, 40% for HL, and 7% for NHL. CONCLUSIONS: To our knowledge, our paper is the first cross-sectional study with multicenter and national data analyzing FP rate in cancer men: it suggests an efficient pathway for men to FP before cancer treatment, compared to previously published studies. Although sperm banking rate in 15-49 years-old men could definitely be improved, further studies should evaluate the information given to patients before gonadotoxic treatments, the factors associated with the absence of sperm banking and whether this lack of referral induces a loss of chance for these men.

RéSUMé: CONTEXTE: Chez les hommes de 15 à 49 ans, les principaux cancers sont le cancer du testicule (CT) et les lymhomes (L): la congélation de spermatozoïdes éjaculés est utilisée en première intention pour leur préservation de fertilité (PF) avant traitement du cancer. Notre objectif était d'analyser le taux de PF chez les hommes de 15 à 49 ans diagnostiqués avec un CT ou un L en 2018 en France. Nous avons réalisé une étude nationale transversale descriptive du taux de congelation de spermatozoïdes chez les hommes âgés de 15 à 49 ans diagnostiqués avec un CT, un L de Hodgkin (LH) ou un L non-Hodgkinien (LNH). A partir des données de l'Institut National du Cancer (INCa) de 2018, nous avons extrait l'incidence estimée de CT et de L en France métropolitaine. A partir des données du bilan d'activité 2018 de la Federation Française des CECOS (Centre d'Etude et de Conservation des Oeufs et du Sperme), nous avons extrait le nombre d'hommes avec un CT ou un L qui ont congelé leurs spermatozoïdes. Nous avons enfin estimé la proportion d'hommes de 15 à 49 ans diagnostiqués avec un CT ou un L qui ont congelé leurs spermatozoïdes. RéSULTATS: Chez les hommes de 15 à 49 ans, l'INCa a estimé en 2018 38 048 nouveaux cas de cancers diagnostiqués en France métropolitaine en 2018: 2 630 CT et 3 913 L (943 LH et 2 970 LNH). Le réseau des CECOS a produit les résultats issus de 26/27 centres métropolitains (taux de réponse de 96%): 1 079 congélations de sperme pour des hommes atteints de CT, 375 pour LH et 211 pour LNH. Nous avons estimé que le taux de congelation de spermatozoïdes de 2018 en France était de 41% pour le CT, 40% pour le LH et 7% pour le LNH. CONCLUSIONS: A notre connaissance, notre travail est la première étude transversale multicentrique de données nationales analysant le taux de PF chez les hommes atteints de cancer: il suggère un parcours patient efficace pour la PF des hommes avant traitement d'un cancer, par rapport aux études précédemment publiées. Bien que le taux de PF chez les hommes puisse certainemen être amélioré, des études futures devraient évaluer l'information donnée aux patients avant traitement gonadotoxique, les facteurs associés à l'absence de PF et si le défaut d'adressage au CECOS induit un perte de chance pour ces hommes. MOTS-CLéS: Chimiothérapie, Radiothérapie, Oncofertiité, Azoospermia, Paternité.

Case report of apoptosis in testis of four AZFc-deleted patients: increased DNA fragmentation during meiosis, but decreased apoptotic markers in post-meiotic germ cells.

AZFc deletions of the Y chromosome are the major known genetic cause of spermatogenetic failure. Meiotic studies have shown a prevalence of synaptonemal complex fragmentation and an excess of early-stage sperm cells, suggesting that the maturation block could involve apoptosis. We present a prospective and observational study of apoptotic markers in the sperm of four AZFc-deleted patients and two non-obstructive azoospermic controls without an AZFc deletion. Polycaspases assays and terminal deoxynucleotidyl transferase dUDP nick-end labelling (TUNEL) assays were combined to evaluate the incidence of apoptosis in pre-meiotic, meiotic and post-meiotic germs cells identified, respectively, using anti-melanoma-associated antigen A4 (MAGE-A4), anti-synaptonemal complex protein 3 (SCP3) and anti-sperm acrosome membrane-associated protein 1 (SPACA1) antibodies. We detected apoptosis at all stages of AZFc-deletion spermatogenesis. Using the caspase assay, the incidence of positive cells was found to be heterogeneous for pre-meiotic (from 4.8 to 84.5%) and meiotic stages (from 7.9 to 57.6%), while for post-meiotic cells, the mean incidence was 6% in AZFc-deleted patients compared with 26.5% in controls (P < 0.05). Using the TUNEL assay, the mean percentage with DNA fragmentation for meiotic cells was 54.0% in AZFc-deleted patients compared with 20.3% in controls (P < 0.05), while the percentage of TUNEL-positive post-meiotic cells ranged from 5.3 to 44.7%. Spermatocyte loss in AZFc-deleted patients occurs via the apoptotic pathway. In post-meiotic cells, the lower incidence of apoptosis in testis from three of the four AZFc-deleted patients, compared with controls, is consistent with AZFc deletions having little negative impact on sperm quality.

Thermal male contraception: A study of users' motivation, experience, and satisfaction.

PURPOSE: The aim of this study is to evaluate the motivations, experience, and acceptability of thermal male contraception (TMC) in male partners of couples requesting the use of TMC as the only couple contraceptive. MATERIALS AND METHODS: To the 72 men of couples seeking male contraception and using TMC between 2011 and 2019, we suggested an anonymous online survey (93 questions) exploring population characteristics, contraceptive histories, motivations for choosing TMC, patient experience at the successive phases of use, relations with partner and environment, and satisfaction with this method. RESULTS: Sixty-seven men agreed to participate (93% response rate); 63 responses were complete and were analyzed (94% participation rate). The main motivations for choosing TMC were "not using hormones" (n = 59/63, 94%) and using a method regarded as "natural" (n = 49/63, 78%). Most of the men surveyed (68%) adopted the method in less than 2 weeks. During the contraception use phase (n = 59 men), they described significantly improved sexual satisfaction, compared to that experienced with their previous contraceptive methods, and they reported high confidence (100% rather/totally confident partner) and support (88% rather/totally supporting partner) from their partner. Most men (n = 35/59, 59%) also reported improved self-esteem. The main negative point was discomfort, reported by 24% of the men. The overall satisfaction score of using this method was 3.78 ± 0.46/4, and 100% of the men reported that they would recommend the method to other men. DISCUSSION AND CONCLUSION: Men using TMC successfully assumed the responsibility for and performed a daily task to provide couple contraception. This positive evaluation, together with the already published contraceptive efficacy and reversibility of TMC, should encourage the development of this method.

Subfertile patients underestimate their risk factors of reprotoxic exposure.

BACKGROUND: Exposure of men and women to environmental reprotoxic agents is associated with impaired fertility and pregnancy rates after assisted reproductive treatment (ART). Nevertheless, such exposures are generally not systematically assessed in current practice before ART and subfertile men are generally less explored than women. Our objective was to study subfertile men and women's level of knowledge about reprotoxic agents, their perception of their own risk factors and the correlation between perceived and identified circumstances of exposure. RESULTS: In our public university hospital, 390 subfertile patients (185 men and 185 women) requiring assisted reproduction technique (ART) treatment, completed a self-report questionnaire before consultation, in order to assess patients' knowledge of reprotoxic exposures, sources of information about them and perception of their own circumstances of exposure. Then a standardized questionnaire was used by the physician during the consultation to estimate domestic, environmental and occupational risk factors of reprotoxic exposures (RFRE). We compared the patients' perception of exposure with the estimated RFRE. The reprotoxic agents knowledge score of patients was 61%. Their main sources of information were the media (40%), the internet (22%) and gynecologists (15%). The standardized questionnaire identified RFRE in 265/390 patients (68%); risk factor was statistically more frequent in men (77%) than in women (59%) (p < 0.05). In total, 141 of the 265 patients with identified RFRE (53%) were aware of their risk factor of reprotoxic exposure. CONCLUSION: We identified risk factors of reprotoxic exposures in the majority of subfertile patients, more frequently in men than in women, and half of patients were not aware of their exposures. Patients' main sources of information were extra medical. Efforts should be made to inform patients, especially men, about potential reprotoxic exposure and to enhance medical training about reprotoxic agents, as recommended by international guidelines. The detection and correction of environmental exposures in subfertile men could improve their fecundity, but also their general health, which has been shown to be poorer than health of fertile men.

RéSUMé: CONTEXTE: L'exposition des hommes et des femmes à des agents reprotoxiques environnementaux est. associée à une atération de leur fertilité et des taux de grossesse après assistance médicale à la procreation (AMP). Néanmoins, ces expositions ne sont généralement pas recherchées en pratique courante avant AMP et les hommes infertiles sont généralement moins explorés que les femmes. Notre objectif était d'analyser le niveau de connaissance des hommes et des femmes infertiles sur les expositions environnementales reprotoxiques, leur perception de leurs propres facteurs de risque et la correlation entre les expositions reprotoxiques perçues et celles identifiées. RESULTATS: Dans notre centre hospitalier universitaire, 390 patients infertiles (185 hommes et 185 femmes) nécessitant un traitement d'AMP ont complété un auto-questionnaire avant la consultation, afin d'évaluer leurs connaissances sur les expositions reprotoxiques, leurs sources d'information sur ce sujet, et leur perception de leurs propres expositions. Puis, lors de la consultation, le médecin utilisait un questionnaire standardisé pour estimer leurs facteurs de risque d'exposition reprotoxique (FRER) domestiques, environnementaux et professionnels. Nous avons comparé la perception par les patients de leurs propres expositions reprotoxiques avec le FRER estimé par le médecin. Le score de connaissance des agents reprotoxique des patients était de 61%. Leurs sources d'information principales étaient les medias (40%), internet (22%), et les gynécologues (15%). Le questionnaire standardisé identifiait un FRER chez 265/390 patients (68%); les FRER étaient significativement plus fréquents chez les hommes (77%) que chez le femmes (59%)(p < 0.05). Au total, 141 patients sur les 265 avec un FRER identifié étaient conscients de leur FRER. CONCLUSION: Nous avons identifié des facteurs de risque d'exposition reprotoxiques chez la majorité des patients infertiles, plus fréquemment chez les hommes que chez les femmes, et la moitié des patients n'étaient conscients de ces expositions. Les principals sources d'information des patients étaient extra-médicales. Des efforts sont nécessaires pour informer les patients, en particulier les hommes, sur les potentielles expositions reprotoxiques comme souligné par les recommandations internationales. La detection et la correction des expositions environnementales chez les hommes infertiles pourraient améliorer leur fécondité, mais aussi leur santé, qui a été démontrée comme moins bonne que celle des hommes fertiles.

In Vitro Co-Exposure to CeO2 Nanomaterials from Diesel Engine Exhaust and Benzo(a)Pyrene Induces Additive DNA Damage in Sperm and Cumulus Cells but Not in Oocytes.

Benzo(a)pyrene (BaP) is a recognized reprotoxic compound and the most widely investigated polycyclic aromatic hydrocarbon in ambient air; it is widespread by the incomplete combustion of fossil fuels along with cerium dioxide nanomaterials (CeO2 NMs), which are used in nano-based diesel additives to decrease the emission of toxic compounds and to increase fuel economy. The toxicity of CeO2 NMs on reproductive organs and cells has also been shown. However, the effect of the combined interactions of BaP and CeO2 NMs on reproduction has not been investigated. Herein, human and rat gametes were exposed in vitro to combusted CeO2 NMs or BaP or CeO2 NMs and BaP in combination. CeO2 NMs were burned at 850 °C prior to mimicking their release after combustion in a diesel engine. We demonstrated significantly higher amounts of DNA damage after exposure to combusted CeO2 NMs (1 µg·L-1) or BaP (1.13 µmol·L-1) in all cell types considered compared to unexposed cells. Co-exposure to the CeO2 NMs-BaP mixture induced additive DNA damage in sperm and cumulus cells, whereas no additive effect was observed in rat oocytes. This result could be related to the structural protection of the oocyte by cumulus cells and to the oocyte's efficient system to repair DNA damage compared to that of cumulus and sperm cells.

Endometrioma ethanol sclerotherapy could increase IVF live birth rate in women with moderate-severe endometriosis.

OBJECTIVE: To examine the impact of ethanol sclerotherapy (EST) for endometrioma on in vitro fertilization (IVF) cumulative live birth rates (CLBR) in women with moderate-severe endometriosis. METHODS: This retrospective cohort study included women with moderate-severe endometriosis (revised American Fertility Society stage III-IV) and endometrioma who underwent IVF with the ultra-long agonist protocol. We compared two groups: women undergoing EST for endometrioma before IVF (EST group), and women whose endometrioma was left in situ during IVF (No-EST group). The primary outcome was the CLBR per IVF cycle, including fresh and frozen embryo transfers. The secondary endpoints included the complication rate, number of mature oocytes retrieved, clinical pregnancy rate and pregnancy loss rate. RESULTS: Seventy-four women were included in the study, with 37 in the EST group and 37 in the No-EST group, representing 67 and 69 IVF cycles, respectively. The population and cycle characteristics were comparable between the two groups, especially the ovarian response to stimulation. The CLBR was significantly increased in the EST group compared to the No-EST group (31.3% vs. 14.5%, p = 0.03). The clinical and biochemical pregnancy rates were significantly increased in the EST group (37.3% vs. 15.9%, p = 0.01 and 43.3% vs. 23.2%, p = 0.01, respectively). Multivariate analysis revealed a significantly increased chance of live birth in women exposed to EST before IVF with an adjusted OR of 2.68 (95% confidence interval, CI: 1.13-6.36, p = 0.02). In the EST group, we reported one major complication Clavien and Dindo classification grade III, complication involving an ovarian abscess that required a laparoscopic drainage. CONCLUSIONS: EST is an interesting technique to improve IVF success rates in women with moderate-severe endometriosis. EST could be discussed before IVF in infertile women.