Adenomyosis among patients undergoing postpartum hysterectomy for uncontrollable uterine bleeding: A multicenter, observational, retrospective, cohort study on histologically-based prevalence and clinical characteristics.

OBJECTIVE: To assess the prevalence of adenomyosis at pathologic examination, and its association with obstetric complications, peripartum maternal clinical characteristics and neonatal birth weight in patients undergoing postpartum hysterectomy due to postpartum hemorrhage (PPH). METHODS: A multicenter, observational, retrospective, cohort study was carried out including all women who underwent postpartum hysterectomy due to PPH at gestational week 23+0 or later, between January 2010 and May 2023. Patients were categorized into two groups based on the presence of adenomyosis at pathologic examination, and were compared for obstetric complications, peripartum maternal clinical characteristics, and neonatal birth weight. RESULTS: The histologically-based prevalence of adenomyosis in patients undergoing postpartum hysterectomy due to PPH was 39.4%. Adenomyosis was associated with a longer hospitalization time (regression coefficient: 4.43 days, 95% CI: 0.34-8.52, P = 0.034) and a higher risk of hypertensive disorders (OR: 5.82, 95% CI: 1.38-24.46, P = 0.016), threatened preterm labor (OR: 3.34, 95% CI: 1.08-10.31, P = 0.036), urgent/emergency C-section (OR: 24.15, 95% CI: 2.60-223.96, P = 0.005), postpartum maternal complications (OR: 4.96, 95% CI: 1.48-16.67, P = 0.012), maternal intensive care unit admission (OR: 3.56, 95% CI: 1.05-12.05, P = 0.041), and low birth weight neonates (OR: 3.8, 95% CI: 1.32-11.02, P = 0.013). CONCLUSION: In patients undergoing postpartum hysterectomy due to PPH, adenomyosis is a highly prevalent condition among, and is associated with adverse obstetric, maternal, and neonatal outcomes.

Italian multicenter mid-term analysis of laparoscopic lateral suspension in women with pelvic organ prolapse: clinical, sexual and Quality of Life assessment after surgical intervention.

BACKGROUND: The aim of this study was to evaluate effectiveness and safety of laparoscopic lateral suspension in women affected by high grade uterine prolapse associated to anterior defect. The secondary endpoint is to evaluate mid-term impact on Quality of Life and sexual function. METHODS: A multicenter retrospective study on women undergoing laparoscopic lateral suspension for uterine prolapse ≥III stage was performed. We included 174 women, but due to exclusion criteria, 134 patients were enrolled for this study. Preoperative evaluation consisted of an urogynecological interview, clinical exam, 3-day voiding diary and urodynamic testing; the prolapse Quality of Life Questionnaire was used to quantify the impact of prolapse symptoms on Quality of Life and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form, the Female Sexual Function Index and the Female Sexual Distress Scale were administered to evaluate sexual function before surgical intervention and at median follow-up of 3.8 years. RESULTS: We included 134 women with uterine prolapse ≥III stage. All patients underwent laparoscopic lateral suspension, 8 also posterior colporrhaphy and 5 also transobturator tape insertion. POP-Q classification score for anterior and apical compartment showed a significant average decrease. The surveys administered to patients showed an improvement in Quality of Life, an increase in the number of monthly intercourses and a significant improvement in sexual life after surgery. CONCLUSIONS: Laparoscopic lateral suspension for pelvic organ prolapse correction is a safe and effective technique for uterine and anterior associated defect. Quality of Life and sexual function significantly improved after surgery.

NO donors on top of anti-hypertensive therapy reduces complications in chronic hypertensive pregnancies with hypodynamic circulation.

OBJECTIVES: Chronic hypertension is associated with significant adverse maternal and fetal outcomes that appear to be often associated to a hypodynamic circulation. Treatment of hypertensive disorders of pregnancy tailored on maternal hemodynamics might reduce or mitigate these complications. Our purpose was to assess the hemodynamic modifications induced by the addition of NO donors and increased oral fluid intake on top of standard antihypertensive therapy in hypodynamic chronic hypertensive patients. We further evaluated if the possible hemodynamic modification induced by NO donors and increased oral fluid intake might be associated to a reduction of the severity and rate of complications vs. patients on antihypertensive standard treatment. STUDY DESIGN: This was a case-control study of 321 chronic hypertensive patients with a hypodynamic circulation at the echocardiographic evaluation at 24 weeks' gestation. We included 160 controls (standard antihypertensive therapy) and 161 cases (standard therapy + NO donor patches + increased oral fluid intake). Student T test for paired and unpaired data, univariate logistic regression analysis, ROC curve analysis, and Cox Hazards Regression analysis were used as appropriate. RESULTS: At enrollment the hemodynamic parameters were similar between the two groups. After 3-4 weeks stroke volume (77 ± 19 mL vs. 69 ± 19 mL; p < 0.001), and cardiac output (6.2 ± 1.7 L vs. 5.0 ± 1.6 L; p < 0.001) were higher and total peripheral vascular resistance (1465 ± 469 dyne·s·cm-5 vs. 1814 ± 524 dyne·s·cm-5; p < 0.001) was lower in the cases vs controls. Superimposed preeclampsia, preterm delivery before 34 weeks, abruptio placentae, HELLP Syndrome, fetal growth restriction, and perinatal death were more represented in the standard treatment group vs NO treated patients (81% vs 53%; p < 0.001). In particular, the standard treatment group showed 48% fetal growth restriction vs 34% in the NO treated group (p < 0.011). The Cox proportional-hazards regression showed a lower proportion of event-free pregnancies in controls on standard treatment (HR 2.6; 95% CI 2.0-3.5; p < 0.0001), and a prolongation of pregnancies in CH cases complicated by fetal growth restriction taking NO donors (HR 0.29; 95% CI 0.19-0.43; p = 0.0001). CONCLUSIONS: The tailored treatment with NO donors and oral fluids of hypodynamic CH might have positive effects on the reduction or mitigations of adverse outcomes.

Combined treatment with vaginal native tissue repair plus mid-urethral sling or pelvic floor muscle training in patients with anterior defect and occult stress urinary incontinence: quality of life and sexual function analysis.

BACKGROUND: The aim of this study was to compare the efficacy of vaginal native tissue repair (VNTR) combined with tension-free transobturator tape (TVT-O) or pelvic floor muscle training (PFMT) in terms of quality of life (QoL) and sexual function (SF) in women affected by anterior defect and occult stress urinary incontinence (OSUI). METHODS: One hundred forty-seven patients with symptomatic anterior defect with OSUI underwent VNTR. In 71 patients TVT-O was inserted and 76 underwent PFMT after surgery. Clinical exam, 3-day voiding diary and urodynamic testing were evaluated in preoperative and postoperative times. Specific questionnaires were also administered, in order to indagate disease perception and the impact on QoL and SF. RESULTS: Nine patients had postoperative pain in the TVT-O group vs. 0 patients in the PMFT group (P=0.001) and 7 patients reported de novo urgency vs. 3 in the two groups, respectively. At 12 weeks follow-up (FU), the first voiding desire was at 88.12+19.70 mL in VNTR+TOT vs. 102.29+19.13 (P=0.03); the mean number of voids (24 hours) was 9.95±2.66 vs. 6.14±1.77 (P=0.04), respectively. No significant differences in terms of QoL and SF were shown. CONCLUSIONS: This retrospective study suggests that VNTR+TVT-O and VNTR+PMFT have the same efficacy in terms of QoL and SF, with several post-operative complications, even if minor, in patients treated with combined surgery.

Evaluation of the efficacy and safety of single incision sling vs TVT-O in obese patients with stress urinary incontinence: Quality of life and sexual function analysis.

OBJECTIVES: The aim of the study is to demonstrate the best stress urinary incontinence (SUI) surgical technique for women with a Body mass index higher than 30. The results of Transvaginal Tension Free Vaginal Tape-Obturator and Mini-sling surgery were analyzed and compared through both clinical examination and standardized questionnaires at 36 months of follow-up. MATERIALS AND METHODS: This is a retrospective multicenter study over 159 women with SUI who underwent surgery. Seventy-eight women underwent TVT-O and 81 Mini-sling technique. Intra and post-operative complications were recorded. Patients were monitored for 36 months by analyzing symptoms, voiding diary, quality of life and sexual activity through standardized questionnaires. RESULTS: Complications had a low incidence in both groups and inter-group differences were superimposable. Only groin pain was statistically higher after TVT-O than after Mini-sling (12.8% vs1.2%, p = 0.03). At 36 months of follow-up, a statistically significant decrease in Positive stress test (%) and Q-Tip test (grade) was observed in both groups with no differences between them (p = 0.54 and p = 0.32 respectively). The mean number of daily voids was higher after TVT-O (p = 0.04) than after Altis (p = 0.22) with a significant difference in favor of the Altis group (p = 0.03). After 36 months, there were no significant differences between groups in terms of quality of life and sexual activity. PGI-I did not show any difference between groups (p = 0.21). CONCLUSION: TVT-O and Minisling had the same efficacy and results in the surgical treatment of SUI in obese women. Both techniques relieved their symptoms and improved their quality of life without any significant difference except for a lower incidence of post- Mini-sling complications.

Sexual function analysis and clitoral vascularization in postmenopausal women with genitourinary syndrome treated with ospemifene.

BACKGROUND: The aim of this study was to evaluate the efficacy of ospemifene in the Vaginal Health Index (VHI), in the vulvovaginal vascular perfusion, and to assess its impact on quality of life and sexual function. METHODS: Among 52 eligible patients, 43 consecutive postmenopausal patients affected by vulvo-vaginal atrophy (VVA), or genitourinary syndrome (GSM) were evaluated. VVA evaluation and ultrasound of the vulvo-vaginal vascularization by sampling the Pulsatility Index (PI) of clitoris dorsal artery were performed before and after 3 months-treatment with ospemifene. The 36-Item Short Form Survey (SF-36) for the quality-of-life assessment before and after 3 months were available for all women; instead, Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS) questionnaires for the sexual function evaluation were performed for sexually active women in the study. The Patient Impression of Global Improvement (PGI-I) after 3 months of treatment was also calculated. RESULTS: The number of sexually active women significantly increased after 3 months (26 [60.46%] vs. 35 [81.39%]; P=0.01). The mean number of intercourses during the treatment increased (12.87±3.43 vs. 15.79±3.12, P=0.03). The PI of clitoris dorsal artery has significantly changed before and after treatment respectively (PI [1.69±0.42 vs. 1.28±0.45, P=0.001] RI [0.74±0.11 vs. 0.54±0.15, P=0.001]). The FSFI, FSDS and SF-36 Questionnaires scores showed a significant improvement after 3 months. VHI and PI were the independent factors of a lower FSFI after 3 months of treatment at multivariate analysis. CONCLUSIONS: Ospemifene improve the VHI and vulvovaginal vascular perfusion demonstrating a positive impact on sexual function and quality of life.

Sequential combined approach in patients with mixed urinary incontinence: surgery followed by posterior tibial nerve stimulation.

AIM: The aim of the study is to demonstrate the efficacy of sequential combined treatment with Transobturator Tape (TOT) followed by Posterior Tibial Nerve Stimulation (PTNS) in patients with Mixed Urinary Incontinence (MUI); quality of life and patients' satisfaction was also assessed. METHODS: Retrospective analysis on women affected by MUI with prevalent Stress Urinary Incontinence (SUI) component. Women, divided in 2 groups, underwent different treatments, TOT vs TOT+PTNS. Population was assessed by medical history, previous pelvic surgery, clinical exam, urodynamic exams, pelvic ultrasound examination, and questionnaires (The International Consultation on Incontinence Questionnaire Short Form, Overactive Bladder Questionnaire, Health Related Quality of Life) comparing them before and after 12 weeks after treatment. RESULTS: 112 women were enrolled in the study. The mean age was 57.96±7.34 in the first group(N=60) and 58.29±6.14 in the second group(N=52). Peak flow (ml/s) statistically improved after treatment, 22.23±4.29 (TOT) vs 24.81±5.8 (TOT+PTNS). First voiding desire(ml) improved significantly between the two groups 108.72±19.24 vs 142.43±19.98. Maximum cystometric capacity (ml) in the TOT group at 12-weeks was 328.76±82.44 vs TOT+PTNS group of 396.26±91.21. Detrusor pressure at peak flow(cmH2O) showed a greater improvement in TOT+PTNS than TOT alone 14.45±6.10 vs 11.89±54.49. At 12-week, urinary diary and quality of life improved in terms of urgent urination events, mean number of voids, urge symptoms and nocturia events. The Patient Impression of Global Improvement (PGI-I) after 3 months was better in combined group. CONCLUSIONS: Combined and sequential TOT+PTNS is more effective compared to TOT alone in MUI patients with prevalent SUI component.

Laparoscopic stripping versus endometrioma ethanol sclerotherapy in women with endometrioma awaiting IVF: a long-term analysis of ovarian reserve and pregnancy outcome.

BACKGROUND: The aim of this study was to compare ovarian reserve, oocytes quality and pregnancy outcome of endometrioma treatment by laparoscopic stripping (LS) versus endometrioma ethanol sclerotherapy (EST) in infertile women awaiting in-vitro fertilization (IVF). METHODS: Retrospective analysis was performed. Twenty-three women underwent EST and 26 women LS. Intra- and postoperative complications were recorded. The women were followed-up for 36 months for cyst recurrence, oocytes quality and pregnancy outcome. Serum anti-Müllerian hormone (AMH) levels after treatment were measured to observe the impact on the ovarian reserve. Women's satisfaction was investigated with PGI-I. RESULTS: During follow-up, there were 3 endometriomas recurrences after LS and none after EST. Six months after treatment AMH was 3.17±2.15 in EST vs. 2.22±1.97 in LS, P=0.045. Symptoms' improvement was comparable. No intraoperative complications occurred. In the LS group the postoperative complications were significantly higher. After IVF cycles, the quality of the retrieved oocytes was the same. In EST group, clinical pregnancy (48.1% vs. 19.6%) and live birth rates (36.5% vs. 14.3%) were significantly increased compared to LS. Women's satisfaction was comparable at PGI-I. Both EST and the presence of an endometrioma sized 6 cm or less proved to be independent factors of a better live birth rate in multivariate analysis. CONCLUSIONS: EST efficacy was greater than LS for endometrioma. Ovarian function was well preserved. Hospital stay was shorter, fewer complications occurred. Pregnancy outcome was better after EST.

Mature Ovarian Teratoma: Neurological Implications in a Young Woman.

Anti-NMDAR encephalitis is an autoimmune syndrome associated with antibodies against NMDA receptors. In some cases, it is associated with various tumors; one of them is ovarian teratoma, which mostly affects women below the age of 30 years. Here, we report a case of ovarian teratoma associated with anti-NMDAR encephalitis treated with both laparoscopic surgery and immunotherapy. Multidisciplinary approach is the cornerstone for the management of this syndrome.

The p63 C-terminus is essential for murine oocyte integrity.

The transcription factor p63 mediates distinct cellular responses, primarily regulating epithelial and oocyte biology. In addition to the two amino terminal isoforms, TAp63 and ΔNp63, the 3'-end of p63 mRNA undergoes tissue-specific alternative splicing that leads to several isoforms, including p63α, p63ß and p63γ. To investigate in vivo how the different isoforms fulfil distinct functions at the cellular and developmental levels, we developed a mouse model replacing the p63α with p63ß by deletion of exon 13 in the Trp63 gene. Here, we report that whereas in two organs physiologically expressing p63α, such as thymus and skin, no abnormalities are detected, total infertility is evident in heterozygous female mice. A sharp reduction in the number of primary oocytes during the first week after birth occurs as a consequence of the enhanced expression of the pro-apoptotic transcriptional targets Puma and Noxa by the tetrameric, constitutively active, TAp63ß isoform. Hence, these mice show a condition of ovary dysfunction, resembling human primary ovary insufficiency. Our results show that the p63 C-terminus is essential in TAp63α-expressing primary oocytes to control cell death in vivo, expanding the current understanding of human primary ovarian insufficiency.

Optimization of the viability of stem cells derived from umbilical cord blood after maternal supplementation with DHA during the second or third trimester of pregnancy: study protocol for a randomized controlled trial.

BACKGROUND: Umbilical cord blood (UCB) is an important source of hematopoietic stem cells (HSCs). However, the concentration of cells in cord blood units is limited and this may represent the main restriction to their therapeutic clinical use. The percentage of metabolically active stem cells provides a measure of the viability of cells in an UCB sample. It follows that an active cellular metabolism causes a proliferation in stem cells, offering an opportunity to increase the cellular concentration. A high cell dose is essential when transplanting cord stem cells, guaranteeing, in the receiving patient, a successful outcome.This study is designed to evaluate the impact of docosahexaenoic acid (DHA) supplementation in pregnant women, in order to increase the quantity and viability of the cells in UCB samples. METHODS/DESIGN: The metabolic demand of DHA increases in the course of pregnancy and reaches maximum absorption during the third trimester of pregnancy. According to these observations, this trial will be divided into two different experimental groups: in the first group, participants will be enrolled from the 20th week of estimated stage of gestation, before the maximum absorption of DHA; while in the second group, enrolment will start from the 28th week of estimated stage of gestation, when the DHA request is higher. Participants in the trial will be divided and randomly assigned to the placebo group or to the experimental group. Each participant will receive a complete set of capsules of either placebo (250 mg of olive oil) or DHA (250 mg), to take one a day from the 20th or from the 28th week, up to the 40th week of estimated gestational age. Samples of venous blood will be taken from all participants before taking placebo or DHA, at the 20th or at the 28th week, and at the 37th to 38th week of pregnancy to monitor the level of DHA. Cell number and cellular viability will be evaluated by flow cytometry within 48 hours of the UCB sample collection. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Register: ISRCTN58396079. Registration date: 8 October 2013.

Molecular basis of thyrotropin and thyroid hormone action during implantation and early development.

BACKGROUND: Implantation and early embryo development are finely regulated processes in which several molecules are involved. Evidence that thyroid hormones (TH: T4 and T3) might be part of this machinery is emerging. An increased demand for TH occurs during gestation, and any alteration in maternal thyroid physiology has significant implications for both maternal and fetal health. Not only overt but also subclinical hypothyroidism is associated with infertility as well as with obstetric complications, including disruptions and disorders of pregnancy, labor, delivery, and troubles in early neonatal life. METHODS: We searched the PubMed and Google Scholar databases for articles related to TH action on ovary, endometrium, trophoblast maturation and embryo implantation. In addition, articles on the regulation of TH activity at cellular level have been reviewed. The findings are hereby summarized and critically discussed. RESULTS: TH have been shown to influence endometrial, ovarian and placental physiology. TH receptors (TR) and thyrotropin (thyroid-stimulating hormone: TSH) receptors (TSHR) are widely expressed in the feto-maternal unit during implantation, and both the endometrium and the trophoblast might be influenced by TH either directly or through TH effects on the synthesis and activity of implantation-mediating molecules. Interestingly, due to the multiplicity of mechanisms involved in TH action (e.g. differential expression of TR isoforms, heterodimeric receptor partners, interacting cellular proteins, and regulating enzymes), the TH concentration in blood is not always predictive of their cellular availability and activity at both genomic and nongenomic level. CONCLUSIONS: In addition to the known role of TH on the hormonal milieu of the ovarian follicle cycle, which is essential for a woman's fertility, evidence is emerging on the importance of TH signaling during implantation and early pregnancy. Based on recent observations, a local action of TH on female reproductive organs and the embryo during implantation appears to be crucial for a successful pregnancy. Furthermore, an imbalance in the spatio-temporal expression of factors involved in TH activity might induce early arrest of pregnancy in women considered as euthyroid, based on their hormonal blood concentration. In conclusion, alterations of the highly regulated local activity of TH may play a crucial, previously underestimated, role in early pregnancy and pregnancy loss. Further studies elucidating this topic should be encouraged.

Schauta-Amreich Operation vs Piver II Procedure with Pelvic Lymphadenectomy for Cervical Cancer.

INTRODUCTION: The aim of this study was to compare two groups of patients with early stage cervical cancer who underwent either abdominal or vaginal surgery, in terms of post-operative findings and survival. MATERIALS AND METHODOLOGY: 55 patients with diagnosed cervical cancer were retrospectively selected for this study. They were preoperatively staged according to FIGO criteria. Forty four patients had disease between stages Ib and IIa with no evidence of extra-pelvic lymph node involvement and 10 patients had stage ≥ IIb. RESULTS: Of the 55 patients, 17 had been operated by Schauta-Amreich radical vaginal hysterectomy and 38 by Piver type II abdominal hysterectomy. No significant statistical differences have been found between two groups about age (median age was 49 for Schauta and 54 for Piver p=0.494) and parity of the patients (Median parity was 2 (range: 0-5) for Piver II group and 1 (range: 0-4) for Schauta group (p=0.607)) and about histotype and stage of the cervical cancer (34 patients with squamous cell carcinoma among Piver II Group vs 16 patients from Schauta Group; 4 women with adenocarcinoma from Piver II Group vs 1 subject from the Schauta Group; p value 1.000). Among the two groups there were significant statistical differences regarding the mean operative time (86 ± 28 minutes for Vaginal surgery and 115 ± 31 minutes for Abdominal surgery, p=0.038) and the average hospital stay (8.65 ± 4.42 days for abdominal surgery and 5.65 ± 2.3 days for vaginal surgery, p=0.020). Significant statistical difference was reported as regarding adjuvant RT, increased in the Piver II group with respect to the Schauta group (22 vs 4 pts; p=0.028). The survival rate at 5-years was without significant difference between the two groups (23 patients frof Piver II Group vs 11 patients from Schauta Group, p=0.510). DISCUSSION: This study confirms the benefits of the Schauta-Amreich vaginal radical hysterectomy in terms of hospital stay, mean operative time and early complications. CONCLUSION: We believe that this surgery is a plausible alternative to radical abdominal hysterectomy and could be considered to be a valid approach for the treatment of patients with cervical neoplasms, but still randomized trials are needed on this topic with respect to the ethical issues involved.

Total vascular resistance and left ventricular morphology as screening tools for complications in pregnancy.

We evaluated the predictive value of elevated total vascular resistance on the outcome of pregnancy in normotensive high-risk primigravidas with bilateral notching of the uterine artery Doppler. A total of 526 high-risk primigravidas referred to the obstetrics outpatient clinic of Tor Vergata University with bilateral notching of the uterine artery at 20 to 22 weeks' gestation were submitted to a maternal echocardiographic examination and uterine artery Doppler evaluation at 24 weeks' gestation. Blood pressure was recorded at the time of the examination, total vascular resistance was calculated, and the geometric pattern of the left ventricle was assessed. Patients were followed until the end of pregnancy to detect fetal/maternal adverse outcomes (gestational hypertension, preeclampsia, abruptio placentae, fetal growth restriction, perinatal death, etc). A total of 111 of the 526 pregnancies showed a bilateral notch at 24 weeks' gestation, and 97 had an adverse outcome (18.44%). The best independent predictor for maternal and fetal complications was total vascular resistance (odds ratio: 91.25; 95% CI: 39.64 to 210.05; P<0.001). The cutoff value was 1400 dynes x s x cm(-5), with a sensitivity and a specificity of 89% and 94%, respectively. A high relative wall thickness of the left ventricle (>0.37; odds ratio: 2.47; 95% CI: 1.12 to 5.44) and a hypertrophized ventricle (left ventricular mass >130 g; odds ratio: 2.52; 95% CI: 1.12 to 5.64) were also independent predictors (P<0.05). Echocardiography might identify at 24 weeks' gestation patients who subsequently develop maternal and fetal complications through the assessment of maternal hemodynamics and left ventricular geometry.

C-peptide and insulin levels at 24-30 weeks' gestation: an increased risk of adverse pregnancy outcomes?

OBJECTIVE: The hypothesis was that fasting C-peptide and insulin values, during an oral glucose tolerance test (OGTT), might allow an estimation of the increased risk for gestational hypertension (GH) and fetal macrosomia. STUDY DESIGN: Two-hundred and six consecutive patients were submitted to an OGTT. Thirty-five developed gestational hypertension and 29 delivered large-for-gestational-age (LGA) newborns. Plasma glucose levels (mg/dl) and insulin levels (microU/ml) were measured fasting and after 60, 120 and 180 min C-peptide fasting levels (ng/ml) were also measured. RESULTS: Twenty-five patients were excluded, 181 were enrolled. According to the OGTT, 143 patients were classified as normal, 26 were found affected by gestational diabetes (GD) mellitus, and 12 had impaired gestational glucose tolerance (IGGT). Hypertensive women exhibited higher 60 and 120 min insulin values than the normotensive group (128.3+/-69.9 microU/ml versus 86.2+/-58.3 microU/ml, P<0.05; 104.9+/-66.4 microU/ml versus 78.7+/-56.5 microU/ml, P<0.05).C-peptide cut-off at 2.9 ng/ml resulted predictive for patients delivering large-for-gestational-age newborns (OR=3.42, 95% CI=1.59-7.39). CONCLUSIONS: C-peptide and insulin may be used as indicators of risk for the development of complications in late pregnancy.

Low fatty acid amide hydrolase and high anandamide levels are associated with failure to achieve an ongoing pregnancy after IVF and embryo transfer.

Human reproduction is a rather inefficient process, yet the molecular reasons for this inefficiency remain unknown. IVF and embryo transfer (IVF-embryo transfer) also results in a high frequency of implantation failures and early spontaneous abortions. Here we show that the anandamide (AEA)-degrading enzyme, fatty acid amide hydrolase (FAAH), had significantly lower activity (46 +/- 17 versus 161 +/- 74 pmol/min per mg protein) and protein content (0.10 +/- 0.03 versus 0.23 +/- 0.06 units) in lymphocytes of IVF-embryo transfer patients who failed to achieve an ongoing pregnancy than in those who become pregnant, and this was paralleled by a significant increase in blood AEA (4.0 +/- 2.2 pmol/ml and 0.9 +/- 1.0 pmol/ml respectively). The blood levels of the other endocannabinoid, 2-arachidonoylglycerol, or of the AEA congener, N-palmitoylethanolamine, which are metabolized by enzymes different from FAAH, was not different between the pregnant and nonpregnant women, nor was there any difference in the activity of the AEA membrane transporter or the amounts of cannabinoid receptors in lymphocytes. Taken together with the reported negative effects of AEA on embryo implantation, this study indicates that low FAAH activity and subsequent increased AEA levels in blood might be one of the causes of implantation failure or pregnancy loss, thereby leading to a better understanding of the pathophysiological and therapeutic implications of endocannabinoids in human fertility.