Exposure to heavy metals during pregnancy related to gestational diabetes mellitus in diabetes-free mothers.

Evidence is cumulating on the adverse health effects of environmental exposures on health of the fetus and the childbearing mothers. Among mother's conditions, gestational diabetes mellitus has been considered rarely in spite of its importance for both mother and child. We determined the role of maternal exposure to lead (Pb), cadmium (Cd) and manganese (Mn) to gestational diabetes mellitus (GDM) on diagnosed GDM and impaired glucose tolerance (IGT) in diabetes-free mothers from the French EDEN mother-child cohort. 623 pregnant women without pre-existing diabetes were included in the study. GDM and IGT were diagnosed by a gynecologist during consultations after blood analysis. Pb, Cd and Mn were measured in second-trimester blood samples. Associations between ln-transformed concentrations of metals and GDM and IGT respectively were examined using multiple logistic regression analysis adjusted for potential confounders. The prevalences of GDM and IGT were 7.1% and 10.1% respectively. After adjustment for confounders, Cd was statistically related to having had a diagnosis of GDM or IGT (Adjusted Odds-Ratio (AOR): 1.61, 1.05-2.48), and Pb to GDM at borderline significance (AOR: 1.65, 0.82-3.34). Our findings add to the growing evidence supporting the role of maternal exposure to heavy toxic metals that persist longtime in the environment as a risk factor for GDM.

Premature progesterone rise on day of hCG negatively correlated with live birth rate in IVF cycles: An analysis of 1022 cycles.

OBJECTIVE: To investigate the relationship between serum P levels on the day of hCG administration and pregnancy outcomes in patients undergoing IVF. DESIGN: Retrospective study. SETTING: Teaching hospital. PATIENTS: A total of 1022 IVF-ICSI cycles, frozen embryo transfer excluded. INTERVENTION(S): Patients-all types of responder - underwent IVF with agonist or antagonist protocols. Clinical outcomes of IVF were analyzed according to plasma P levels. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rates. RESULTS: We proposed a serum P level of 1.57ng/ml on day of hCG as a threshold for all types of responders and all protocols combined. Ongoing implantation rates were not affected by elevated progesterone. Live birth rate was inversely associated with serum P levels on day of hCG and more miscarriages were associated with P>1.57ng/ml. We have not found the progesterone>1.57ng/ml on the day of hCG as a prognostic factor for pregnancy. CONCLUSION(S): Elevated P level on the day of hCG administration negatively influence live birth rate and is correlated to an increase of miscarriage. The detrimental effect of P elevation on pregnancy seems not to be related substantially to endometrium receptivity. Thus, despite a comparable clinical pregnancy rate and an initial implantation rate, we demonstrate more spontaneous abortion and it would seem that the effect of progesterone is later.

Women infected with human immunodeficiency virus type 1 have poorer assisted reproduction outcomes: a case-control study.

OBJECTIVE: To compare the efficacy of assisted reproductive technology (ART) in women infected with human immunodeficiency virus type 1 (HIV-1) versus HIV-negative controls. DESIGN: Retrospective case-control study. SETTING: University hospital ART unit. PATIENT(S): Eighty-two women infected with HIV-1 and 82 women as seronegative controls. INTERVENTION(S): Ovarian stimulation, oocytes retrieval, standard in vitro fertilization (IVF) or intracytoplasmic sperm injection, embryo transfer. MAIN OUTCOME MEASURE(S): Clinical pregnancies and live-birth rates. RESULT(S): After oocyte retrieval, all women infected with HIV-1 infected were matched 1:1 to HIV-negative controls according to the following criteria: date of ART attempt, age, parity, main cause of infertility, ART technique, and rank of attempt. Only the first IVF cycle during the study period was considered for each couple. We found no statistically significant differences between the two groups for ovarian stimulation data, fertilization rate, or average number of embryos transferred. The clinical pregnancy rate per transfer was statistically significantly lower for the cases compared with the controls (12% vs. 32%), as were the implantation rate (10% vs. 21%) and the live-birth rate (7% vs. 19%). CONCLUSION(S): In one of the largest studies to pair six factors that influence the results of ART, HIV infection in women was associated with poorer outcomes after ART. These results suggest that women with controlled HIV-1-infection should be counseled not to delay ART in cases of self-insemination failure or other causes of infertility. Fertility preservation by vitrification of oocytes in women whose pregnancy should be delayed may be an important future consideration.

Laparoscopic surgery for distal tubal occlusions: lessons learned from a historical series of 434 cases.

OBJECTIVE: To evaluate the success rate of laparoscopic neosalpingostomy and the factors affecting the results in terms of intrauterine pregnancy (IUP), delivery (DEL), and ectopic pregnancy (EP). DESIGN: Retrospective analysis of prospectively recorded data. SETTING: Private practice. PATIENT(S): A total of 434 consecutive infertile patients from 21 to 42 years old with a follow-up of more than 10 years. INTERVENTION(S): Laparoscopic neosalpingostomy. MAIN OUTCOME MEASURE(S): Intrauterine pregnancy, delivery, and EP rates obtained without requiring IVF. Statistical analysis includes univariate and multivariate analysis and crude and actuarial success rates. RESULT(S): Just over one-quarter (28.8%) of the patients presented an IUP, 24.4% delivered, and 9% presented with an EP. The 5-year actuarial rate of delivery was 37%. This rate was largely dependent on the tubal stage (stage 1: 53.1%; stage 2: 43.1%; stage 3: 24.0%; stage 4: 23.1%). Forty-three percent of the expected IUPs started in the first year, and 75% started in the first two years. Multivariate analysis found some poor-prognosis patterns for tubal stage 3 (odds ratio [OR] 0.24), tubal stage 4 (OR 0.28), repeated neosalpingostomy (OR 0.168), previous EP (OR 0.202), severe adhesion stage (OR 0.211), and positive chlamydial serology (OR 0.515). Eversion with sutures provides nonsignificantly better results (OR 1.63) compared with eversion with coagulation. CONCLUSION(S): Neosalpingostomy must not be proposed in selected cases according to the tubal stage, adhesion stage, and chlamydial serology. When neosalpingostomy is performed, fimbrial eversion with sutures provides slightly better results.

Markers of hepatitis delta virus infection can be detected in follicular fluid and semen.

BACKGROUND: Hepatitis delta virus (HDV) is a satellite of HBV and needs this latter's envelope for its morphogenesis and propagation. An estimated 5-20% of HBV-infected patients are also infected with HDV. No studies have ever been performed to determine the presence of HDV in follicular fluid (FF) and semen of HDV-infected patients. OBJECTIVES: To investigate the presence of HDV markers in the FF or in the semen of two HDV-infected patients. DESIGN: Two unrelated HDV-infected patients, a woman and a man pursuing in vitro fertilization (IVF), participated in this study. FF was collected after analysis of oocyte retrieval. The supernatant of seminal plasma (SP) and the final pellet (FP) were fractionated from freshly ejaculated semen. Serological and molecular markers of HDV infection were searched for in these different samples. RESULTS: The woman was infected with an HDV-7 genotype strain and her HDV plasma viral load (VL) was 6 log copies/mL. HDV antibodies and RNA were also detected in the FF, however the RNA VL value there was lower by more than 4 log. The man was infected with an HDV-1 strain and his plasma VL was 6.7 log copies/mL. Total anti-HDV antibodies were positive in the serum, in the SP and in the FP, while IgM were detected only in the serum. However, HDV RNA was negative in the SP and in the FP. CONCLUSION: HDV markers can be found in the follicular fluid or in the semen of infected patients.

Colouterine fistula after polymyomectomy: a case report.

INTRODUCTION: Colouterine fistula is a very rare condition; most cases described in the literature are secondary to complications of diverticulitis in elderly patients. CASE PRESENTATION: We report the case of a 34-year-old African woman who presented with a colouterine fistula secondary to polymyomectomy, which was diagnosed in the setting of severe endometritis. She had a Hartmann procedure and abundant irrigation of her abdominal and uterine cavities followed by placement of a double drainage in order to preserve fertility. This is the first case of a conservative management of the uterus in such conditions. CONCLUSION: Conservative surgery in colouterine fistula should be discussed as an alternative to hysterectomy in young infertile women.

Impact of obesity on the results of fertility-sparing management for atypical hyperplasia and grade 1 endometrial cancer.

OBJECTIVES: The aim of the present study was to evaluate the impact of obesity on reproductive and oncologic outcomes on the success of fertility-sparing management. METHODS: This retrospective multicenter cohort study included women treated conservatively for atypical hyperplasia (AH) and endometrial cancer (EC) to preserve fertility. Five inclusion criteria were defined: (i) the presence of AH or grade 1 EC confirmed by two pathologists; (ii) adequate radiological examination before conservative management; (iii) available body mass index (BMI) at the beginning of treatment; and (iv) a minimum follow-up time of six months. RESULTS: Forty patients fulfilled the inclusion criteria (17 had EC, and 23 had AH), mean age and BMI were 33 years and 29kg/m(2) respectively. Among the 15 obese patients, after medical treatment, 10 patients responded (67%) and three relapsed, whereas in the 25 non-obese patients, 19 responded (76%) and three relapsed (p=0.72). The overall pregnancy rate and follow-up time were 35% and 35 months respectively. Among the 15 obese patients, after medical treatment, two patients became pregnant, whereas in the 25 non-obese patients, 12 became pregnant (p=0.04). CONCLUSION: Despite similar response and recurrence rates, our results suggest that fertility-sparing management for AH and EC is associated with a lower probability of pregnancy in obese patients.

Timing of intermittent seminal HIV-1 RNA shedding in patients with undetectable plasma viral load under combination antiretroviral therapy.

It was demonstrated that combination antiretroviral therapy (cART) reduces the HIV-1 viral load (VL) in the blood and the seminal compartment. Some studies have reported that the seminal HIV-1 VL is undetectable in individuals with an undetectable blood plasma viral load (bpVL) under cART. However, some recent studies have demonstrated that seminal HIV-1 RNA may still be detected, and potentially infectious, even in the case of an undetectable bpVL. The aim of this retrospective study was to determine the detection rate of a seminal VL and whether shedding could be intermittent over a very short time. From January 2006 to December 2011, 88 HIV-1 infected men, enrolled in an Assisted Reproduction program, provided 306 semen samples, corresponding to 177 frozen sperm samples (two samples delivered at a one-hour interval (n = 129) or one sample (n = 48)). All enrolled men were under cART, with an undetectable bpVL for more than 6 months. HIV-1 RNA was quantified in seminal plasma using a Roche COBAS Ampliprep COBAS TaqMan HIV-1 test. Seminal HIV-1 RNA was detected in 23 samples (7.5%) from 17 patients (19.3%). This detection rate was stable over years. With regards to the freezing of two samples delivered at a one-hour interval, the proportion of discordance between the first and second samples was 9.3% (12/129). Our results confirm the intermittent shedding of HIV-1 in semen. While this finding has been shown by studies examining longer time intervals, to our knowledge, this has never been demonstrated over such a short time interval.

Pregnancy outcomes among women with Marfan syndrome.

OBJECTIVE: To determine cardiac and obstetric outcomes among women with Marfan syndrome (MS) whose pregnancies were managed in accordance with the French national guidelines. METHODS: A descriptive analysis was conducted for a prospective cohort of 18 women with MS who gave birth in the maternity unit of Bichat-Claude Bernard Hospital, Paris, France, between January 1, 1998, and May 31, 2011. The study hospital was the national referral center for MS and related diseases. RESULTS: A total of 22 pregnancies were recorded among the study cohort. Of these, 21 were managed according to the national guidelines. One woman who was referred to the study hospital during late pregnancy was not managed according to the national guidelines; this patient experienced aortic dissection at 37 weeks. In the cohort, aortic diameter did not increase significantly during pregnancy. Vascular fetal growth restriction was observed in 7 (31.8 %) of the pregnancies. Cesarean delivery was planned for 17 (77.3%) of the pregnancies. CONCLUSION: Risk of aortic dissection was low among a cohort of pregnant women with MS who were managed according to the French national guidelines.

Intracytoplasmic morphologically selected sperm injection (IMSI) after repeated IVF or ICSI failures: a prospective comparative study.

OBJECTIVE: Sperm morphology plays a significant role in assisted reproductive technologies and is associated with high implantation rates. The objective of this study was to evaluate the outcome of intracytoplasmic morphologically selected sperm injection (IMSI) after repeated failures of conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) techniques. STUDY DESIGN: In a prospective study in which couples acted as their own controls, 75 infertile couples were offered IMSI after at least two previous IVF or ICSI failures. The main outcome measures were embryo quality and number of blastocysts obtained. RESULTS: The percentage of top quality embryos obtained at day 2 was increased in IMSI compared to IVF/ICSI cycles (89.8% versus 79.8%; p=0.009). Extended embryo culture was possible in 41.3% of IMSI cycles versus 26.7% of IVF/ICSI cycles (p=0.04), and the mean number of blastocysts obtained was higher in IMSI cycles (1.5±1.9) than in IVF/ICSI cycles (1.0±1.2) (p=0.03). Moreover, IMSI resulted in clinical pregnancy and birth rates of respectively 29.3% and 18.6%. CONCLUSION: After two or three IVF/ICSI failures, IMSI seems to give better embryo quality and more blastocysts, which allow more embryo transfers at the blastocyst stage. This study supports the use of sperm ultramorphology examination as an independent test to be proposed after repeated IVF or ICSI failures.

Advantages of the two-step embryo transfer strategy in human IVF/ICSI cycles.

The aim of this study was to evaluate the advantages of the two-step embryo transfer (ET) strategy combining a day 2/3 ET with a day 5/6 blastocyst transfer. In an observational comparative study, 400 infertile women were enrolled from two assisted reproductive technology (ART) units according to inclusion criteria: age below 42 years and at least three embryos obtained on day 2 thus allowing an extended in vitro culture. Two groups were defined according to the ET strategy adopted: group 1 had a two-step ET; and group 2 had a day 2/3 ET with (subgroup 2a) or without (subgroup 2b) blastocysts cryopreserved on day 5/6. Live birth rate was significantly higher in group 1 than in subgroups 2a and 2b (36.5% versus 29.4% and 13.4%, respectively; p < 10(-3)). Multiple pregnancy rates were comparable between groups. After adjusting on major prognostic factors, the two-step ET strategy was still associated with a significantly higher live birth rate than the day 2/3 ET (OR = 2.23; 95% CI: 1.32-3.77). The two-step ET provides better live birth rates than the cleavage-stage ET. It does not increase multiple pregnancy rates if the number of embryos transferred is limited. It also prevents cycle loss when embryos fail to develop into blastocysts.

Association between maternal blood cadmium during pregnancy and birth weight and the risk of fetal growth restriction: the EDEN mother-child cohort study.

The objective of this study is to investigate the potential effect of maternal environmental cadmium (Cd) exposure on birth weight and fetal growth restriction (FGR). A total of 901 pregnant women from the EDEN cohort study were enrolled from two maternity units. Blood Cd was measured at mid-pregnancy and associations with birth weight and FGR were analyzed. Maternal Cd levels were associated with reduced birth weight in the offspring of women who smoked during pregnancy (b=-113.7; p=0.001). Smoking during pregnancy and maternal blood Cd concentrations had comparable effects on FGR incidence (OR 1.89; 95% CI: 1.00-3.58 and OR=1.41; 95% CI: 1.00-1.99, respectively). This study highlights the effect of Cd toxicity on fetal growth through the probable accumulation and transmission of this metal through the placenta. The close relationship between blood Cd levels and smoking habits indicates that Cd may be a relevant biomarker for smoking toxicity on fetal development.

Safety of transient abdominal ovariopexy in patients with severe endometriosis.

OBJECTIVE: To evaluate complications of transient ovariopexy performed to reduce adhesions in patients with severe endometriosis. METHODS: A bicentric retrospective study involved 193 consecutive patients who underwent laparoscopic surgery for severe endometriosis at 2 French university hospitals from 1997 to 2009. At the end of surgery, unilateral or bilateral transient ovariopexy was performed on 297 ovaries. Immediate (e.g. reproducibility, tolerance, and hospital stay) and long-term (evaluated via vaginal access to the ovaries, ovarian function, and ovarian vascularization) complications were assessed. RESULTS: The technique, which was easy and reproducible, did not increase hospital stay and was well tolerated. There were 2 (0.7%) immediate complications. There was no difference in ovarian accessibility before and after surgery (177/183 [96.7%] vs 176/183 [96.1%]). Potential vaginal oocyte retrieval for in vitro fertilization was possible for all patients. The antral follicle count and the pulsatility index of suspended ovaries were not different from those of contralateral unsuspended ovaries. Endometrioma excision did not modify these results. CONCLUSION: The short- and long-term safety results of transient ovariopexy for adnexal adhesions in patients with severe endometriosis were encouraging.

Progestin treatment of atypical hyperplasia and well-differentiated adenocarcinoma of the endometrium to preserve fertility.

AIM: To evaluate the outcome of a cohort of young women treated with progestin for fertility-sparing management of endometrial atypical hyperplasia (AH) and endometrial carcinoma (EC). This retrospective multicentre cohort study included women under the age of 40 years treated conservatively for AH and EC to preserve fertility using progestin for at least 3 months. Four inclusion criteria were defined: (i) the presence of AH or grade 1 EC confirmed by two pathologists (including a reference pathologist); (ii) the use of conservative management for fertility sparing; (iii) adequate radiological examination before conservative management; and (iv) a minimal follow-up time of one year. RESULTS: Twenty-two patients fulfilled the inclusion criteria (8 had EC, and 14 had AH). After progestin treatment, 17 patients responded. Among the 17 patients who experienced remission, three also experienced disease relapse. One patient initially diagnosed with AH experienced progression of her disease to stage IIIA EC. Ten pregnancies were achieved in eight patients. CONCLUSION: Fertility-sparing management using progestin offers the opportunity to fulfil maternal desires in young patients diagnosed with AH and EC. However, progression of the disease is possible and close follow-up is needed.

Correlation between DNA defect and sperm-head morphology.

The utility of sperm DNA testing remains controversial. However, it may be helpful in couples with unexplained failures of multiple assisted reproductive techniques and/or recurrent abortions. This study analysed 10,400 spermatozoa of 26 patients for sperm-head morphology with high-magnification microscopy, DNA fragmentation and sperm chromatin decondensation. A significant negative correlation was demonstrated between sperm-parameters and abnormal sperm-head morphology as assessed by high magnification (score 0 according to this study's classification): concentration (r=-0.41; P=0.03), motility (r=-0.42; P=0.03), morphology (r=-0.63; P=0.0008). No correlation was found with DNA fragmentation. However, the sperm chromatin-decondensation rate of score-0 spermatozoa was twice as high as the controls (19.5% versus 10.1%; P<0.0001). This observation suggests that score-0 spermatozoa should not be selected for intracytoplasmic sperm injection.

[Fertility sparing management of endometrial adenocarcinoma and atypical hyperplasia: a literature review]. / Traitement conservateur du cancer et des hyperplasies atypiques de l'endomètre en vue de préserver la fertilité : revue de la littérature.

In endometrial carcinoma (EC) and atypical hyperplasia (AH) diagnosed in childbearing years, the principle of uterine sparing consists in prescription of antigonadotropic treatment to obtain the remission of the endometrial lesion and allow pregnancy, always with a close follow-up looking for progression or persistence of the tumour. Studies evaluating this strategy have suggested the safety of such an approach, but numerous questions remain unanswered, like those concerning the type and the duration of treatment, and the systematic use of Assisted Reproductive Technologies… We performed a critical literature review in order to analyse patients and tumoral characteristics, treatment management and the results of fertility sparing strategy. This review shows that fertility sparing management of AH and intramucous EC permits to obtain pregnancy in one third of candidates. Few disease-related deaths have been reported after this management. One-third of patients experienced progression lesion beyond the endometrium, but generally limited to the myometrium. Progestins have been widely evaluated in this indication and provide an overall remission rate of 80% with a recurrence risk of 25%.

Diagnosis and management of an immature teratoma during ovarian stimulation: a case report.

INTRODUCTION: The discovery of a mature teratoma (dermoid cyst) of the ovary during ovarian stimulation is not a rare event. Conversely, we could not find any reported cases of immature teratoma in such a situation. Clinical and ultrasound arguments for this immature form are scarcely or poorly evaluated. CASE PRESENTATION: We describe the case of a 31-year-old Caucasian woman with primary infertility, who developed an immature teratoma during an in vitro fertilization ovarian stimulation cycle. CONCLUSIONS: Ultrasound signs of an atypical cyst during ovarian stimulation allowed us to adopt a careful medical attitude and to adapt the required surgical oncological treatment.

Fertility-sparing management of grade 2 and 3 endometrial adenocarcinomas.

We report four cases of grade 2 and 3 endo-metrial adenocarcinomas managed conservatively in order to preserve fertility. In the literature, seven other cases have been reported. We discuss the management of these cases and compared the carcinologic and fertility outcomes with fertility-sparing management of grade 1 endometrial adenocarcinoma.

Infertile women with deep and intraperitoneal endometriosis: comparison of fertility outcome according to the extent of surgery.

STUDY OBJECTIVE: This study was undertaken to ascertain whether the incidence of spontaneous pregnancy is increased in infertile women with deep and intraperitoneal endometriosis undergoing extensive surgery compared with those undergoing only intraperitoneal surgery. DESIGN: Retrospective case control study (Canadian Task Force classification II-1). SETTING: University teaching hospital. PATIENTS: Infertile women under the age of 40 years with deep and intraperitoneal endometriosis and no other associated major infertility factors. Only patients with at least 1 year of postoperative follow-up were included. INTERVENTIONS: Intraperitoneal surgery only (group 1) or extensive surgery (group 2) according to a shared decision-making approach. MEASUREMENTS AND MAIN RESULTS: Among the 34 women in group 1, 6 became pregnant, compared with 8 of the 41 women who had extensive surgery (12-month cumulative probabilities, 24.8% and 11.4%, respectively, and 24-month cumulative probabilities, 24.8% and 23.2%, respectively; p = .82). Perioperative surgical complication rate was higher in group 2 (6/41 versus 0/34; p = .02). CONCLUSION: Extensive surgery for intraperitoneal and deep endometriosis in infertile women does not modify global fertility outcome but is associated with a higher complication rate.