Antinuclear antibodies positivity in women in reproductive age: From infertility to adverse obstetrical outcomes - A meta-analysis.

This systematic review and meta-analysis were designed to identify possible correlations between isolated serum antinuclear antibody (ANA) and (i) infertility in the context of in-vitro fertilization (IVF), (ii) idiopathic recurrent pregnancy losses (RPL), and (iii) second/ third trimester pregnancy complications. We performed a systematic review and meta-analysis of the literature in PubMed Library database from inception to March 2022 following PRISMA guidelines. Our pooled results showed a lower pregnancy rate among ANA-positive women undergoing IVF/ICSI compared to ANA-negative women undergoing the same procedures (279/908 versus 1136/2347, random effect, odds ratio -OR- 0.50, 95% confidence interval -CI- 0.38-0.67, p 0.00001, I2 = 58%). We also reported a higher miscarriage rate among ANA-positive compared to ANA-negative women (48/223 versus 109/999, random effect, OR: 3.25 95% CI: 1.57-6.76, p = 0.002, I2 = 61%) and a lower implantation rate (320/1489 versus 1437/4205, random effect, OR: 0.51, 95% CI: 0.36-0.72, p = 0.0001, I2 = 78%). Regarding RPL, pooled results demonstrated a higher prevalence of ANA-positivity in RPL women compared to controls (698/2947 versus 240/3145, random effect, OR: 3.22, 95% CI: 2.12-4.88, p 0.00001, I2 77%), either using > 2 or > 3 pregnancy losses threshold for defining RPL. Heterogeneity of reporting outcome did not allow a quantitative analysis and led to no clear demonstration of an effect of serum ANA on the incidence of stillbirth, preeclampsia and hypertensive disorders. In conclusion, the unfavorable effect of serum ANA was observed in women following IVF. Similarly, ANA were associated with the risk of RPL, while data were unconclusive in terms of late pregnancy complications.

Comparison between X-ray-hysterosalpingography and 3 Tesla magnetic resonance-hysterosalpingography in the assessment of the tubal patency in the cause of female infertility.

OBJECTIVES: XR-hysterosalpingography currently represents the gold standard for tubal pathology evaluation. Magnetic resonance-HSG is an innovative technique. With our study, we aim to comprehend if and how MR-HSG, compared to traditional XR-HSG, could give us this additional information in the diagnostic/therapeutic process. MATERIALS AND METHODS: This study included 19 patients between 30 and 42 years old (average age 37.7) affected by infertility. Patients underwent contextually both XR-HSG and MR-HSG, using a single catheterization. The dynamic MR-HSG exam consisted a MR sequence during contrast administration through the cervical catheter. RESULTS: Both XR-HSG and MR-HSG documented that 15 of the 19 patients had bilateral tubal patency, while four patients had monolateral tubal patency. However, MR-HSG allowed us to diagnose additional findings: Two active endometriosis foci in adnexal localization and a condition of adenomyosis A unicornuate uterus malformation A submucous uterine myoma near the tubal ostium A decrease of the ovarian reserve in a patient So MR-HSG could potentially detect in 10/19 (52%) women the cause of their infertility, compared to 4/19 (21%) detected with XR-HSG and about 30% of women would have resulted as false negatives if we only used XR-HSG. Finally, with a questionnaire, we demonstrated that MR-HSG is less painful than XR-HSG. CONCLUSIONS: These data thus confirm that XR-HSG and MR-HSG present the same diagnostic of assessing tubal patency. We also demonstrated that MR-HSG is able to detect further collateral findings that could likewise be a possible therapeutic target and it could possibly become the new gold standard in female infertility diagnostics.

Clinical significance of endometrial abnormalities: an observational study on 1020 women undergoing hysteroscopic surgery.

BACKGROUND: The overall clinical significance of the finding of endometrial abnormalities in predicting premalignant/malignant endometrial lesions is still incompletely determined. For this reason the management, surgical or expectant, of women in which an endometrial abnormality has been detected is debated. METHODS: This retrospective study was carried out on 1020 consecutive women, 403 premenopausal and 617 postmenopausal, who underwent operative hysteroscopy in a University Hospital for suspected endometrial abnormalities, which were detected by transvaginal ultrasound (TVS) and/or office hysteroscopy. In these women, the clinical characteristics and findings at TVS and hysteroscopy were evaluated in relation to the presence/absence of premalignant/malignant endometrial lesions at pathology report. RESULTS: The clinical characteristics considered were significantly different when the study women were compared according to their menopausal status. Premalignant/malignant lesions were found in 34/1020 (3.33%) women. Complex hyperplasia with atypia and endometrial cancer were detected in 22 (2.15%) and 12 (1.17%) cases, respectively. The postmenopausal women had a significantly higher risk of premalignant/malignant lesions than premenopausal women (O.R. = 5.098 [95% C.I.: 1.782-14.582], P < 0.005). This risk was even higher when abnormal uterine bleeding (AUB) was present (O.R. = 5.20 [95% C.I.: 2.38-11.35], P < 0.0001). The most significant associations with premalignant/malignant endometrial lesions were BMI, AUB in postmenopause, overall polyp size, atypical aspect of endometrial polyps at hysteroscopy, postmenopausal status, diabetes mellitus and patient age. CONCLUSIONS: The results of the present study suggest that the proper, aggressive or expectant, management of endometrial abnormalities should take into account both ultrasonographic and hysteroscopic findings together with the specific clinical characteristics of the patients.

Successful preterm pregnancy in a rare variation of Herlyn-Werner-Wunderlich syndrome: a case report.

BACKGROUND: Herlyn-Werner-Wunderlich syndrome (HWWS) is an uncommon congenital anomaly of the female urogenital tract, characterised by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. We reported the difficult pregnancy course complicated by an extremely rare and unique case of this syndrome associated with ectrodactyly, a clinical combination never described in literature. CASE PRESENTATION: A 28- year-old nulliparous woman previously diagnosed for HWWS associated with ectrodactyly of the right foot and with a history of abdominal left hemi-hysterectomy, ipsilateral salpingectomy, vaginal reconstruction when she was an adolescent. She suffered from threats of abortion in the first trimester, recurrent urinary tract infections during all pregnancy. At 33 weeks + 5 days of gestational age, she was hospitalized for premature rupture of the membranes and uterine contractions and a caesarean section was performed because of breech presentation. Postpartum period was complicated by a pelvic abscess resolved with parental antibiotic therapies. CONCLUSIONS: Our literature review shows an unusual aspect in our case: HWWS is not classically associated with skeletal anomalies. Moreover, the most frequent urogenital side affected is the right, not left side as in this woman. Preterm spontaneous rupture of membranes and fetal abnormal presentation represent frequent complications and probably post-caesarean infections are related to pregnancies in the context of this syndrome.

The diagnosis of PCOS in young infertile women according to different diagnostic criteria: the role of serum anti-Müllerian hormone.

PURPOSE: To diagnose polycystic ovary syndrome (PCOS) in young infertile women using different diagnostic criteria. To define serum anti-Müllerian hormone (AMH) cutoff values for PCOS definition. To investigate the correlation between AMH and body mass index (BMI). METHODS: Retrospective case-control study. A total of 140 infertile women (age 21-35 years) were enrolled. PCOS was defined according to the National Institutes of Health (NIH) criteria, the Rotterdam consensus criteria and the Androgen Excess and PCOS Society (AE-PCOS) criteria. ROC curve analysis was performed to define AMH thresholds for PCOS definition according to the three different diagnostic criteria. Correlation between AMH and BMI was investigated. RESULTS: The prevalence of PCOS under the NIH criteria, the Rotterdam criteria and the AE-PCOS criteria was 27.1, 40 and 29.3%, respectively. The optimal thresholds of AMH to distinguish NIH PCOS from infertile controls was 5.20 ng/ml (AUC = 0.86, sensitivity 79%, specificity 80%); the best cutoff to detect Rotterdam PCOS was 4.57 ng/ml (AUC = 0.85, sensitivity 78%, specificity 81%); a cutoff of 4.85 ng/ml (AUC = 0.85, sensitivity 80%, specificity 78%) defined PCOS women according to AE-PCOS criteria. The prevalence of the syndrome became 37.1, 44.3 and 39.2% according to the three criteria, respectively, using AMH threshold between 4.57 and 5.20 ng/ml as an alternative to antral follicle count and/or hyperandrogenism. CONCLUSION: Anti-Müllerian hormone may reconcile the three diagnostic criteria and allow the PCOS diagnosis in women with mild symptoms. No significant correlation was found between AMH and BMI in PCOS women and controls.

Anti-Müllerian hormone levels and spontaneous pregnancy in women undergoing surgery for benign ovarian cysts.

This prospective study had the objective to compare anti-Müllerian hormone (AMH) serum levels among women with endometriomas and those with other benign ovarian cysts and verify a possible correlation between the AMH post-operative decline and the achievement of pregnancy. The study included 57 women undergoing laparoscopic surgery. Serum levels of AMH were measured preoperatively and at 6 and 12 months postoperatively. AMH serum levels decreased in both endometriomas and other benign cysts, but significant recovery was reported only in endometriomas (p = .029). Through an interview, information on reproductive outcome was obtained. The secondary endpoint was to identify other predictors of spontaneous pregnancy onset. After surgery 27 women attempted to conceive. At 18-months follow-up, 12 of them got pregnant, with a live birth of 37%. We did not record statistically significant differences in reproductive outcome between women with AMH serum levels lower and higher than 1.1 ng/ml (41.7 and 53.3% respectively). There was no statistically significant difference in AMH serum levels between pregnant and non-pregnant women, neither before nor after surgery. AMH did not appear to have a predictive role on reproductive outcome.

Role of vaginal estradiol pretreatment combined with vaginal misoprostol for cervical ripening before operative hysteroscopy in postmenopausal women.

OBJECTIVE: To assess the efficacy and safety of vaginal misoprostol after a pretreatment with vaginal estradiol to facilitate the hysteroscopic surgery in postmenopausal women. METHODS: In this observational comparative study, 35 control women (group A) did not receive any pharmacological treatment,26 women (group B) received 25 µg of vaginal estradiol daily for 14 days and 400 µg of vaginal misoprostol 12 hours before hysteroscopic surgery, 32 women (group C) received 400 µg of vaginal misoprostol 12 hours before surgery. RESULTS: Demographic data were well balanced and all variables were not significantly different among the three groups. The study showed a significant difference in the preoperative cervical dilatation among the group B (7.09±1.87 mm), the group A (5.82±1.85 mm; B vs. A, P=0.040) and the group C (5.46±2.07 mm; B vs. C, P=0.007). The dilatation was very easy in 73% of women in group B. The pain scoring post surgery was lower in the group B (B vs. A, P=0.001; B vs. C, P=0.077). In a small subgroup of women with suspected cervical stenosis, there were no statistically significant differences among the three groups considered. No complications during and post hysteroscopy were observed. CONCLUSION: In postmenopausal women the pretreatment with oestrogen appears to have a crucial role in allowing the effect of misoprostol on cervical ripening. The combination of vaginal estradiol and vaginal misoprostol presents minor side effects and has proved to be effective in obtaining satisfying cervical dilatation thus significantly reducing discomfort for the patient.

The role of serum anti-Müllerian hormone (AMH) in the hormonal diagnosis of polycystic ovary syndrome.

BACKGROUND: The study was performed to validate the threshold for anti-Müllerian hormone (AMH) that suggests the presence of polycystic ovaries in women with polycystic ovary syndrome (PCOS). METHODS: This prospective observational study included 59 infertile women: (A) 22 PCOS with hyperandrogenism (HA) and oligo-anovulation, (B) 15 suspected PCOS with either HA or oligo-anovulation and (C) 22 asymptomatic control women. The diagnosis of PCOS was made according to the NIH classification. RESULTS: For serum AMH and follicle number, respectively, the areas under the receiver operating characteristic curve (A versus C) were 0.97 and 0.93. The best compromise between specificity (95% and 91%) and sensitivity (95% and 82%) was obtained with threshold values of 33 pmol/l and 13 follicles, respectively. Using a serum AMH > 33 pmol/l as a surrogate for either HA or oligo-anovulation in group B would lead to the diagnosis of PCOS in seven (46.6%) patients from this group. CONCLUSIONS: Our data confirms that the AMH assay has a high diagnostic potential, providing that an appropriate threshold is used. AMH measurement may be included as an ultimate diagnostic criterion for the diagnosis of PCOS when either HA or anovulation is missing and/or when no reliable antral follicle count can be obtained.

Sequential low-dose step-up and step-down protocols with recombinant follicle-stimulating hormone in polycystic ovary syndrome: prospective comparison with step-down protocol.

PURPOSE: To assess the differences in follicular development comparing two sequential low-dose step-up and step-down protocols (A: 37.5 IU/day, B: 75 IU/day) with a step-down protocol (C: 150 IU/day) using recombinant human follicle stimulating hormone (rFSH) in women with polycystic ovarian syndrome (PCOS). METHODS: In this prospective observational comparative study, 60 PCOS women were treated with one of the three protocols for only one cycle. RESULT(S): Monofollicular development was similar among the three protocols but the total number of follicles >10 mm in diameter was significantly lower in group A (1 ± 0.94 vs 6.3 ± 2.45 vs 8.6 ± 4.45; P = 0.001 A vs B; P < 0.001 A vs C). Cycle cancellation rate was higher in protocol A and in protocol C because of no ovarian response and excessive multifollicular development, respectively. The total amount of rFSH for complete cycle was significantly lower in protocol A (P = 0.02 A vs B; P = 0.007 A vs C). No mild or severe hyperstimulation syndrome (OHSS) was observed. CONCLUSION(S): A and B protocols seem to be a more effective approach than the step-down protocol. In both groups, the pregnancy rate for started cycle was the same. Protocol A has allowed the development of a lower number of small follicles, single pregnancies, but an excessive number of cancelled cycles occurred. In protocol B no cycle cancellation occurred, though the total rFSH dosage was significantly higher than the protocol A and two twin pregnancies were observed.

Inherited thrombophilia in infertile women: implication in unexplained infertility.

Many studies evaluating a possible relationship between inherited thrombophilia and the etiology of unexplained infertility have been performed recently. No significant difference in the prevalence of three genetic mutations associated with the increased risk of thrombophilia (Factor V Leiden G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase [MTHFR] C677 T) was found in 100 infertile women with unexplained infertility when compared with 200 control fertile women without an infertility history.

Homologous intrauterine insemination in controlled ovarian hyperstimulation cycles: a comparison among three different regimens.

OBJECTIVE: The objective was to assess the efficacy of double intrauterine insemination (IUI) over a single periovulatory IUI in patients undergoing controlled ovarian hyperstimulation with low-dose recombinant follicle stimulating hormone (rFSH) combined with human chorionic gonadotropin (HCG). STUDY DESIGN: Ninety-four infertile women were randomly assigned to three groups; in group A (38 patients, 47 cycles) a single IUI was performed 36 h after HCG administration combined with timed intercourse the day of HCG administration; within group B (43 patients, 48 cycles) IUI alone was performed 36 h after HCG administration; in group C (39 patients, 43 cycles) a double IUI 12 and 36 h after HCG administration was performed. RESULTS: The mean age and the causes of infertility were similar between the three groups. The number of follicles greater than 15 mm on the day of HCG administration and the overall dose of rFSH required per cycle was not significantly different among the groups. The pregnancy rate (PR) per cycle and per patient was 14.9% and 18.4% in group A, 10.4% and 11.6% in group B, 20.9% and 23.1% in group C, respectively. There was no statistically significant difference in PR among the three groups. CONCLUSION: In rFSH/HCG cycles, two IUIs performed 12 and 36 h after HCG administration do not significantly improve pregnancy rates over a single insemination performed 36 h after HCG administration combined with or without timed intercourse the day of HCG administration.