Reconstructive surgery for congenital atresia of the uterine cervix: a systematic review.

The authors discuss the incidence, the embryological development, the classification, the presentation and the treatment options of this rare reproductive tract abnormality. In the past, the treatment proposed almost unanimously was hysterectomy and subsequent construction, when necessary, of a neovagina. In recent decades, numerous experiences of conservative therapies have accumulated that allow the restoration of menstrual function and in some rare cases even the achievement of a pregnancy. However, complications associated with recanalization of the cervix frequently resulted in the need for repeated surgery, risk of serious and sometimes fatal ascending infection. This review aims to analyze the most recent and significant experiences of conservative surgery in this field to provide an accurate picture of the various techniques and their outcomes, especially from the point of view of fertility. Conservative surgery should now be considered as the first-line treatment option. On the other hand, it is not possible to draw conclusions on the superiority of one technique over another among the various conservative options. This would require large series with adequate follow-up, which unfortunately are not available.

The Peritoneal Neovagina after Davydov's Laparoscopic Procedure in Mayer-Rokitansky-Küster-Hauser Syndrome: Morphology and Ultrastructure Investigation of the New Epithelium.

STUDY OBJECTIVE: To investigate the clinical appearance and morphologic and ultrastructural aspects of the mucosa of the peritoneal neovagina after laparoscopic Davydov neovaginoplasty in patients with Mayer-Rokitansky-Küster-Hauser syndrome. DESIGN: The study group was a prospective, observational, experimental cohort of cases treated in the same institution between 2015 and 2019. Patients were followed up at 3, 6, and 12 months after surgery and then every 12 months. SETTING: Single-center academic institution and teaching hospital in Milan, Italy. PATIENTS: Fifty-one consecutive subjects with clinical and imaging diagnosis of Mayer-Rokitansky-Küster-Hauser syndrome surgically treated by the same team and postoperatively followed. INTERVENTIONS: All the subjects underwent the same standardized surgical procedure and thereafter were followed up at 3, 6, and 12 months after surgery and then every 12 months; a minimum follow-up of 12 months was achieved in all cases. Vaginoscopy and Schiller test were performed at each follow-up visit, and a biopsy specimen of the neovagina was obtained in a limited number of patients (6 out of 51) for light microscopy (LM) and scanning electron microscopy (SEM) analysis of the tissue. MEASUREMENTS AND MAIN RESULTS: In vaginoscopy, the neovaginal mucosa appeared homogeneous, smooth, and pink all along the neovaginal tract; the Schiller test detected iodine positivity at different degrees of extension upward from the hymenal ring, starting at 3 months postoperatively with almost complete positivity between 6 to 12 months in all cases. LM demonstrated adequate thickness and differentiation of the new mucosa along with the presence of glycogen storage; SEM revealed an ultrastructural surface appearance very close to normality. The main difference compared with a normal vagina was the reduced presence of vaginal mucosal folds. CONCLUSION: Under different techniques (vaginoscopy, Schiller test, LM, and SEM), a minimum of 6 months after surgery, the peritoneal neovagina epithelium showed aspects comparable to the natal mucosa of the vagina.

Lower urinary tract symptoms in patients with Mayer-Rokitansky-Kuster-Hauser syndrome after neo-vagina creation by Davydov's procedure.

INTRODUCTION: Lower urinary tract symptoms (LUTS) in subjects with Mayer-Rokitansky-Küster-Hauser syndrome treated by Davydov's laparoscopic neo-vaginoplasty were measured. METHODS: Davydov's laparoscopic neo-vaginoplasty was undertaken at the Department of Obstetrics/gynecology, San Raffaele Hospital, Milan, Italy, from November 2015 to July 2017, by two highly qualified surgeons. All women completed the ICIQ-UI Short Form questionnaire before and after treatment. LUTS were scored at recruitment, hospitalization, and 1, 3, 6 and 12 months after surgery. RESULTS: Twenty-one women (mean age 21 years ± 5.9) were operated on with no major complications. Mean surgery duration was 79 min (± 55 min). Before the operation, one patient (1/21; 4.8%) reported occasional urinary loss that persisted after surgery and throughout 12 months of follow-up. After the operation, one patient (1/21; 4.8%) had urinary retention, requiring self-catheterization for 2 weeks. One month after surgery, stress incontinence was recorded in one case (1/19; 5.2%) and urge incontinence in two cases (2/19; 10.5%). At 3-month follow-up, these three patients were free of symptoms. CONCLUSION: The rate of LUTS is lower than that reported by others using alternative surgical procedures. To the best of our knowledge, this is the first report validating LUTS after Davydov's neo-vaginoplasty.

Oocyte Retrieval during Laparoscopic Vaginoplasty to Reduce Invasiveness in the Treatment of Mayer-Rokitansky-Küster-Hauser Syndrome.

STUDY OBJECTIVE: To evaluate the treatment of patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome with a combination of oocyte retrieval and surgical vaginoplasty in a single laparoscopic procedure. DESIGN: A case series. SETTING: The study was conducted at 2 tertiary referral facilities for MRKH syndrome in Milan, Italy, between July 2017 and September 2018. PATIENTS: Eleven patients presented with MRKH and required surgical vaginoplasty while expressing a desire for future fertility. INTERVENTIONS: Two experienced surgeons and an expert in assisted reproductive technology performed concomitant vaginoplasty according to the modified technique of Davydov and laparoscopic oocyte retrieval for gamete cryopreservation. MEASUREMENTS AND MAIN RESULTS: Before the procedure, patients underwent extensive counseling and gave written consent. At the start of surgery, 10.4 ± 4.4 (mean ± standard deviation [SD]) oocytes were retrieved laparoscopically, and 8.8 ± 3.1 (SD) mean mature oocytes were cryopreserved. After oocyte retrieval, the steps of the modified Davydov technique were followed. The total operative time was 116 ± 16 minutes (mean ± SD), and no intraoperative/postoperative complications were observed. CONCLUSION: This is the first report of combined oocyte retrieval and vaginoplasty for patients with MRKH syndrome. The approach was found to be feasible in patients with a desire for future fertility. It is our belief that physicians treating patients with MRKH should refer patients to centers with expertise in both vaginoplasty and assisted reproductive technology.

High yield production and purification of two recombinant thermostable phosphotriesterase-like lactonases from Sulfolobus acidocaldarius and Sulfolobus solfataricus useful as bioremediation tools and bioscavengers.

BACKGROUND: Thermostable phosphotriesterase-like lactonases (PLLs) are able to degrade organophosphates and could be potentially employed as bioremediation tools and bioscavengers. But nowadays their manufacturing in high yields is still an issue that limits their industrial applications. In this work we aimed to set up a high yield production and purification biotechnological process of two recombinant PLLs expressed in E. coli, the wild type SacPox from Sulfolobus acidocaldarius and a triple mutated SsoPox C258L/I261F/W263A, originally from Sulfolobus solfataricus. To follow this aim new induction approaches were investigated to boost the enzyme production, high cell density fermentation strategies were set-up to reach higher and higher enzyme yields up to 22-L scale, a downstream train was studied to meet the requirements of an efficient industrial purification process. RESULTS: Physiological studies in shake flasks demonstrated that the use of galactose as inducer increased the enzyme concentrations up to 4.5 folds, compared to the production obtained by induction with IPTG. Optimising high cell density fed-batch strategies the production and the productivity of both enzymes were further enhanced of 26 folds, up to 2300 U·L- 1 and 47.1 U·L- 1·h- 1 for SacPox and to 8700 U·L- 1 and 180.6 U·L- 1·h- 1 for SsoPox C258L/I261F/W263A, and the fermentation processes resulted scalable from 2.5 to 22.0 L. After being produced and extracted from the cells, the enzymes were first purified by a thermo-precipitation step, whose conditions were optimised by response surface methodology. A following ultra-filtration process on 100 and 5 KDa cut-off membranes drove to a final pureness and a total recovery of both enzymes of 70.0 ± 2.0%, suitable for industrial applications. CONCLUSIONS: In this paper, for the first time, a high yield biotechnological manufacturing process of the recombinant enzymes SacPox and SsoPox C258L/I261F/W263A was set-up. The enzyme production was boosted by combining a new galactose induction approach with high cell density fed-batch fermentation strategies. An efficient enzyme purification protocol was designed coupling a thermo-precipitation step with a following membrane-based ultra-filtration process.

Fetal Doppler changes 1 week after endoscopic equatorial laser for twin-to-twin transfusion syndrome: A longitudinal study.

OBJECTIVE: To investigate sequential Doppler changes in donors and recipients before and 1 week after endoscopic laser for twin-to-twin transfusion syndrome (TTTS) and to examine factors that may be associated with such changes. METHODS: In TTTS pregnancies undergoing laser treatment, we examined fetal Doppler changes before and 1 week postintervention. Intrauterine death rates and preoperative factors were analyzed in relation to Doppler changes. RESULTS: Among 129 (85.4%) donors surviving at 1 week after laser, there was normalization of umbilical artery flow in 26 (72.2%) of 36 cases with preoperative abnormal Dopplers. In the remaining 10 (27.8%) fetuses, abnormal findings persisted. The rate of later intrauterine death was significantly higher in the latter group (6 of 10, 60.0%) compared with fetuses in which Doppler findings normalized (4 of 26, 15.4%; P < .05), with no difference in the rate of severe donor growth restriction between the 2 groups (80.0% vs 65.4%, respectively; P = .688). CONCLUSIONS: In about 70% of TTTS donors with preoperative abnormal umbilical artery Doppler, there was normalization 1 week after endoscopic laser. The incidence of fetal growth restriction was not significantly different in donors with persistence of Doppler abnormalities compared with those with normalized findings.

Mitochondrial DNA copy number in peripheral blood: a potential non-invasive biomarker for female subfertility.

PURPOSE: Low mitochondrial DNA (mtDNA) content in oocytes and in cumulus cells is an indicator of poor oocyte quality. Moreover, initial evidence showed a correlation between mtDNA content in cumulus cells and mtDNA copy number in peripheral blood cells. On these bases, we deemed of interest investigating the correlation between mtDNA copy number in peripheral blood and natural fecundity. METHODS: This is a nested case-control study drawn from a prospective cohort of pregnant women referred for routine first trimester screening for aneuploidies (from 11 + 0 to 12 + 6 weeks of gestation) between January 2012 and March 2013 at the "Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico" of Milan, Italy. Cases were subfertile women who attempted to become pregnant for 12-24 months. Controls were the two subsequently age-matched women who became pregnant in less than 1 year. MtDNA was quantified using real-time PCR and normalized to nuclear DNA. RESULTS: One hundred and four subfertile women and 208 controls were selected. The median (IQR) mtDNA copy number was 95 (73-124) and 145 (106-198), respectively (p < 0.001). The area under the ROC curve was 0.73 (95% CI 0.67-0.79) (p < 0.001). The Youden index was 105 mtDNA copy number. The crude OR for subfertility in women with mtDNA copy number below this threshold was 5.72 (95% CI 3.43-9.55). The accuracy of mtDNA copy number assessment in peripheral blood progressively decreased with increasing female age. CONCLUSIONS: Low mtDNA copy number in peripheral blood is associated with an increased risk of subfertility and may represent a biomarker of natural fecundity.

Alport syndrome and pregnancy: a case series and literature review.

PURPOSE: To assess pregnancy outcome in women with Alport syndrome and the impact of pregnancy on the disease progression. METHODS: We describe one of the largest series of pregnancies in Alport syndrome. Seven pregnancies of six women were monitored by a multidisciplinary team of nephrologists and gynecologists. After delivery, patients were followed for at least 3 years. We compare our results with those in the literature. RESULTS: Pregnancy course was uneventful in the patient with isolated microscopic hematuria. In the other cases, all presenting mild proteinuria at conception, some complications occurred. Proteinuria worsened during the last trimester, reaching nephrotic ranges in five out of six pregnancies and was associated with fluid overload leading to hospitalizations and early delivery. The majority of the newborns had a low birth weight. The two patients with arterial hypertension at conception and twin pregnancy developed pre-eclampsia and renal function deterioration persisted after delivery. The one with pre-pregnancy renal dysfunction reached end-stage renal disease. In the other patients, in which renal function and blood pressure were and remained normal, proteinuria improved after delivery and no signs of disease progression were recorded at last observation. CONCLUSIONS: Our observations suggest that Alport syndrome should be considered a potential risk factor for pregnancy in proteinuric patients due to the development of pre-eclampsia, renal function deterioration, and/or full-blown nephrotic syndrome that results in anasarca, slowing of fetal growth and pre-term delivery. Thus, all women with Alport syndrome should receive pre-conceptional counseling and be kept in close follow-up during pregnancy.

Maternal Subcutaneous and Visceral Adipose Ultrasound Thickness in Women with Gestational Diabetes Mellitus at 24-28 Weeks' Gestation.

OBJECTIVE: To compare the sonographic measurement of maternal subcutaneous and visceral adipose thickness between pregnant women with gestational diabetes mellitus (GDM) and patients with nondiabetic pregnancies. METHODS: Adipose thickness was measured by transabdominal ultrasound in pregnant women attending our antenatal clinics at 24-28 weeks' gestation. All patients underwent a 75-g oral glucose challenge as a diagnostic test for GDM. RESULTS: The study population comprised 56 women with a positive glucose challenge test and 112 nondiabetic pregnancies. Measurements of subcutaneous and visceral adipose tissues were converted into multiples of the median (MoM), adjusted for gestational age. The mean subcutaneous thickness MoM in patients with GDM was significantly higher compared to nondiabetic pregnancies (1.31 vs. 1.07; p = 0.011). Similarly, the mean visceral thickness MoM was higher in women with a positive oral glucose tolerance test compared to controls (1.61 vs. 1.06; p < 0.001). Multivariate logistic regression analysis demonstrated that visceral adipose thickness, but not subcutaneous thickness, was significantly and independently associated with GDM (odds ratio 34.047, 95% confidence interval 9.489-122.166). CONCLUSIONS: Sonographic thickness of maternal visceral adipose tissue at 24-28 weeks' gestation was higher in women with GDM compared to nondiabetic pregnancies, independently from other known risk factors associated with GDM.

Creation of a Neovagina by Laparoscopic Modified Davydov Vaginoplasty in Patients with Partial Androgen Insensitivity Syndrome.

STUDY OBJECTIVE: To evaluate the feasibility, safety, and outcome of laparoscopic modified Davydov vaginoplasty in subjects with partial androgen insensitivity syndrome (PAIS). DESIGN: A retrospective cohort study (Canadian Task Force classification III). SETTING: A tertiary referral center. PATIENTS: Ten continuous patients operated on between October 2008 and May 2014. INTERVENTIONS: Laparoscopic modified Davydov vaginoplasty. The surgical technique was tailored on PAIS subjects who presented a male pelvic anatomy and, frequently, anomalies of the external genitalia. MEASUREMENTS AND MAIN RESULTS: Anatomic success was defined as a neovaginal width allowing the insertion of 2 fingers and a neovaginal length of at least 5 cm. Functional success was defined as the presence of regular sexual intercourse. Laparoscopic modified Davydov vaginoplasty was successfully performed in all patients without surgical complications. At hospital discharge, anatomic success was achieved in all patients. At the 12-month follow-up, anatomic success was achieved in 9 patients and functional success in 7 patients. Two patients with anatomic success did not start any sexual activity by personal choice. One patient had an anatomic failure with a neovaginal length of 2 cm. This patient had not complied with the postoperative use of vaginal dilators. CONCLUSION: This is the first study reporting the outcomes of laparoscopic modified Davydov vaginoplasty in subjects with PAIS. Postoperative long-term outcomes were comparable with those achieved in women with Rokitansky syndrome. The laparoscopic modified Davydov operation may represent the procedure of choice for the creation of a neovagina and the concomitant correction of anomalies of the external genitalia in subjects with PAIS.

Boosted large-scale production and purification of a thermostable archaeal phosphotriesterase-like lactonase for organophosphate decontamination.

Thermostable phosphotriesterase-like lactonases (PLLs) from extremophile archaea, like SsoPox from Sulfolobus solfataricus, are attractive biotechnological tools with industrial applications as organophosphate decontaminants, but their manufacturing still remains an unresolved issue because of the high costs and the low production yields. In this paper, for the first time, an efficient biotechnological process for the production and purification of a recombinant, engineered PLL, SsoPox W263F, expressed in E. coli, has been set up by studying new induction strategies, by designing high cell density cultivations and a new membrane-based downstream process. In fed batches, the enzyme production was boosted of 69-fold up to 4660.0 U L-1 using galactose as inducer in the replacement of IPTG; the process was scalable from 2.5 up to 150 L. By coupling a single thermo-precipitation step and an ultrafiltration process, a total enzyme recovery of 77% with a purity grade of almost 80% was reached.

Fetoscopic Endoluminal Tracheal Occlusion in Fetuses with Severe Diaphragmatic Hernia: A Three-Year Single-Center Experience.

OBJECTIVE: To report on our experience in the prenatal treatment of severe congenital diaphragmatic hernia (CDH) by fetoscopic endoluminal tracheal occlusion (FETO). METHODS: Between 2012 and 2014, FETO was performed at our center in 21 cases of CDH considered to be severe based on sonographic measurement of observed/expected lung-to-head ratio (O/E LHR) and side of the defect. We reported pre- and postoperative ultrasound findings, procedure-related complications, pregnancy outcome and survival at 1-3 years of age. RESULTS: The median gestational age (GA) at balloon insertion was 28.1 weeks (range 26.0-31.1) and the median GA at delivery 34.7 weeks (range 31.6-39.0); delivery before 32 and 34 weeks occurred in 2 (9.5%) and 7 (33.3%) cases, respectively. Postnatal survival at 1-3 years of age in the 17 cases with isolated unilateral CDH was 47.1%. The percentage difference between pre-balloon removal O/E LHR and pre-FETO O/E LHR was significantly higher in survivors compared to neonates who died (40.8 vs. 21.2%, respectively; p < 0.05). CONCLUSIONS: In this study, FETO was associated with an infant survival of 47% in cases with isolated unilateral severe CDH. The post-FETO increase in O/E LHR was higher in fetuses that survived compared to those who died.

Postnatal survival after endoscopic equatorial laser for the treatment of twin-to-twin transfusion syndrome.

BACKGROUND: Endoscopic laser coagulation of placental anastomoses is the first-line treatment for severe twin-to-twin transfusion syndrome. A recent randomized controlled trial reported that laser coagulation along the entire vascular equator was associated with a similar dual survival and survival of at least 1 twin compared with the group that was treated with the selective technique. In addition, there was a significantly lower incidence of postoperative recurrence of twin-to-twin transfusion syndrome and the development of twin anemia-polycythemia sequence in the equatorial group. OBJECTIVE: The purpose of this study was to report on neonatal survival in twin-to-twin transfusion syndrome pregnancies that were treated with endoscopic laser therapy with the use of the equatorial technique and to examine the relationship between preoperative factors and twin loss. STUDY DESIGN: Endoscopic equatorial laser therapy was carried out as the primary treatment for twin-to-twin transfusion syndrome in all consecutive monochorionic diamniotic twin pregnancies that were referred at a single fetal surgery Center over a 4-year period. All visible placental anastomoses were coagulated; additional laser ablation of the placental tissue between the coagulated vessels was carried out. Pre-laser ultrasound data, periprocedural complications, pregnancy outcome, and postnatal survival at hospital discharge were recorded and analyzed. RESULTS: A total of 106 pregnancies were treated during the study period. Median gestational age at laser therapy was 19.7 weeks (range, 15.1-27.6 weeks). There was postoperative recurrence of twin-to-twin transfusion syndrome or the development of twin anemia-polycythemia sequence in 2 (1.9%) and 2 (1.9%) cases, respectively. The survival rates of both and at least 1 twin were 56.6% and 83.0%, respectively. Donor survival was significantly lower compared with the recipient co-twin (64.2% vs 75.5%, respectively; P < .05). The rate of fetal death, which was the most common cause of twin loss, was significantly higher in donors compared with recipient fetuses (23.6% vs 10.4%, respectively; P < .05). In cases with absent or reversed end-diastolic velocity in the donor umbilical artery, dual and donor survival rates were significantly lower compared with the remaining twin-to-twin transfusion syndrome pregnancies (40.0% vs 64.8% and 40.0% vs 76.1%, respectively; P < .05). There were no significant differences between the 2 groups in the survival of at least 1 twin and in the recipient survival. CONCLUSIONS: Endoscopic equatorial laser therapy was associated with a survival of both and at least 1 twin of approximately 55% and 83%, respectively, with a low rate of recurrent twin-to-twin transfusion syndrome and twin anemia-polycythemia sequence. In addition, the preoperative finding of abnormal donor umbilical artery Doppler on ultrasound identified a subgroup of twin-to-twin transfusion syndrome pregnancies with a lower dual survival rate caused by increased intrauterine deaths of donor twins.

Cell-free DNA testing in the maternal blood in high-risk pregnancies after first-trimester combined screening.

OBJECTIVE: The objective of this study was to investigate a strategy for clinical implementation of cell-free DNA (cfDNA) testing in high-risk pregnancies after first-trimester combined screening. METHODS: In 259 singleton pregnancies undergoing invasive testing after first-trimester combined screening, a maternal blood sample was sent to the laboratory Natera for cfDNA testing using a single-nucleotide polymorphism-based methodology. RESULTS: The cfDNA test provided a result in 249 (96.1%) pregnancies and, among these, identified as being at high risk 35 of 36 cases of trisomy 21, 13 of 13 with trisomy 18, five of five with trisomy 13 and three of four with sex chromosome aneuploidies. A policy of performing an invasive test in women with a combined risk of ≥1 in 10 or NT ≥4 mm and offering cfDNA testing to the remaining cases would detect all cases of trisomy 21, 18 or 13, 80% of sex aneuploidies and 62.5% of other defects and would avoid an invasive procedure in 82.4% of euploid fetuses. CONCLUSION: In high-risk pregnancies after combined screening, a policy of selecting a subgroup for invasive testing and another for cfDNA testing would substantially reduce the number of invasive procedures and retain the ability to diagnose most of the observed aneuploidies.

Prenatal ultrasound factors and genetic disorders in pregnancies complicated by polyhydramnios.

OBJECTIVE: The objective of the study is to examine the incidence of chromosomal or genetic abnormalities in pregnancies complicated by polyhydramnios and to assess the value of prenatal ultrasound findings in the prediction of cases associated with such disorders. METHODS: We searched the prenatal records of all patients delivered in our hospital with a diagnosis of polyhydramnios during pregnancy. For each case, maternal characteristics, ultrasound findings, and genetic testing results were recorded. A postnatal follow-up program of at least 6 months, including a clinical assessment by a clinical geneticist, was carried out in all cases. RESULTS: On a total of 195 cases, genetic testing and clinical examination identified a chromosomal or genetic disease in 26 (13.3%) cases. Multivariate analysis demonstrated that significant predictors of a genetic disorder were a deepest vertical pocket of amniotic fluid of ≥13.0 cm (OR 4.306, 95%CI: 1.535-12.079) and reduced fetal movements (OR 25.084, 95%CI: 4.577-137.461), but not the presence of a structural defect. CONCLUSION: A postnatal clinical follow-up program can reveal chromosomal or genetic disorders in about 13% of neonates with a prenatal diagnosis of polyhydramnios. The severity of polyhydramnios and the reduction of fetal movements are independently associated with the presence of such diseases. © 2016 John Wiley & Sons, Ltd.

THE LONG-TERM IMPACT OF CONTROLLED OVARIAN HYPERSTIMULATION ON THYROID FUNCTION.

OBJECTIVE: Evidence on the long-term impact of controlled ovarian hyperstimulation (COH) on thyroid function is scarce. To investigate this, we report on serum thyroid-stimulating hormone (TSH) modifications in euthyroid and hypothyroid women during COH and 3 months after the end of the stimulation cycle. METHODS: Women who underwent in vitro fertilization (IVF) and who did not become pregnant were eligible. Cases were women with treated hypothyroidism and basal serum TSH <2.5 mIU/L. Controls were euthyroid women matched to cases by age and basal serum TSH. Women could be included if serum TSH was available at 4 time points: prior to initiating COH (time 1); at the time of human chorionic gonadotropin (hCG) administration (time 2); 16 days after hCG administration (time 3); and 3 months after the end of the IVF cycle (time 4). RESULTS: Thirty-seven case-control pairs were included. Serum TSH at times 1, 2, 3, and 4 was 1.7 ± 0.6, 3.1 ± 1.4, 3.1 ± 1.3, and 2.7 ± 1.7 mIU/L, and 1.7 ± 0.6, 2.9 ± 1.0, 2.7 ± 1.0, and 1.9 ± 0.7 mIU/L among cases and controls, respectively. A statistically significant difference emerged at time 4 (P<.001). In both groups, serum TSH was higher at time 4 compared to time 1. Serum TSH exceeded the recommended threshold of 2.5 mIU/L at time 4 in 51% of cases (95% confidence interval [CI], 35 to 68%) and in 16% of controls (95% CI, 4 to 28%) (P = .003). CONCLUSION: COH seems to have a long-term impact on TSH levels. The magnitude of this effect is particularly pronounced in hypothyroid women.

Adenomyosis: What the Patient Needs.

A panel of experts in the field of endometriosis expressed their opinions on management options in a 28-year-old patient, attempting pregnancy for 1 year, with severe cyclic pelvic pain and with clinical examination and imaging techniques suggestive of adenomyosis. Many questions this paradigmatic patient may pose to the clinician are addressed, and all clinical scenarios are discussed. A decision algorithm derived from this discussion is also proposed.

Serum Levels of 25-Hydroxyvitamin D and Time to Natural Pregnancy.

AIM: The aim of this study was to evaluate whether natural fertility is related to serum 25-hydroxyvitamin D (25-OH-vitamin D) levels. METHODS: A nested case-control study was designed from a prospective cohort of pregnant women undergoing first trimester screening for aneuploidies. Cases included women seeking pregnancy for 12-24 months. Controls were the subsequent age-matched women conceiving in less than 1 year. We excluded women aged ≥40 or <18 years, those assuming supplementary products that included vitamin D before or during pregnancy, those with irregular menstrual cycles or known causes of subfertility, those conceiving through assisted reproductive techniques or requiring ovarian stimulation and those who were overweight or obese. A quantitative detection of serum 25-OH-vitamin D and patients' interview were performed. RESULTS: Seventy-three cases and 73 matched controls were selected. The mean ± SD serum 25-OH-vitamin D was 21.2 ± 6.8 and 19.7 ± 7.3 ng/ml, respectively (p = 0.16). The number (%) of women with serum levels <20 ng/ml (vitamin D insufficiency) was 34 (47%) and 37 (51%), respectively (p = 0.73). The adjusted OR of longer time to pregnancy in women with vitamin D insufficiency was 0.84 (95% CI 0.42-1.66). CONCLUSIONS: Our study does not support a crucial role of 25-OH-vitamin D in natural fertility.

Prenatal ultrasound predictors of postnatal major cerebral abnormalities in fetuses with apparently isolated mild ventriculomegaly.

OBJECTIVE: We aim to examine the incidence of major cerebral abnormalities on postnatal imaging in cases with isolated mild ventriculomegaly on fetal sonography and to evaluate the relationship between the presence or absence of such defects and prenatal ultrasound factors. METHODS: We searched our databases to identify all cases with mild ventriculomegaly (10-15 mm) and no other major structural abnormalities on prenatal ultrasound, with normal karyotype and no evidence of maternal or fetal infection. For each case, we retrieved data on prenatal ultrasound follow-up, fetal magnetic resonance imaging (MRI), neonatal ultrasound and/or brain MRI, and pregnancy outcome. RESULTS: Postnatal imaging revealed a major cerebral abnormality in 9 (6.9%) of 130 live borns with isolated mild ventriculomegaly on prenatal ultrasound. In six (66.7%) of nine cases, the abnormality was known or suspected prenatally on fetal MRI. Multivariate analysis showed that the only significant contribution to the prediction of major cerebral abnormalities was provided by persistence or progression of ventricular enlargement on serial ultrasound examinations (p = 0.001, odds ratio 21.1 [95% confidence interval: 3.6-122.7]). CONCLUSION: Prenatal ultrasound follow-up identifies fetuses at higher risk for a major cerebral abnormality among cases with isolated mild ventriculomegaly. In cases with persistent or progressive enlargement, fetal MRI and postnatal imaging seem appropriate.

Intrafollicular iron and ferritin in women with ovarian endometriomas.

OBJECTIVE: To evaluate whether iron contained in ovarian endometriomas can diffuse through the cyst wall and negatively affect ovarian function. DESIGN: Prospective case series. SETTING: Infertility unit in an academic setting. POPULATION: Thirty-nine infertile women with unilateral endometriomas who underwent in vitro fertilization. METHODS: Iron and ferritin assessments in pools of follicular fluids obtained from affected and contralateral intact gonads. MAIN OUTCOME MEASURES: Iron and ferritin concentrations. RESULTS: Follicular fluid iron content did not differ between the two gonads. The median [interquartile range (IQR)] follicular concentrations in the affected and unaffected ovaries were 59 (IQR 44-74) and 59 (IQR 47-73) µg/dL, respectively (p = 0.77). Conversely, ferritin concentration was significantly higher in affected gonads. The median (IQR) concentrations of ferritin in the affected and unaffected ovaries were 57 (IQR 31-146) and 33 (IQR 23-67) µg/mL, respectively (p = 0.026). When considering together the 78 studied ovaries, no significant correlations emerged between follicular iron and ferritin and variables reflecting ovarian responsiveness and oocyte developmental competence. CONCLUSIONS: Iron may diffuse from ovarian endometriomas into the adjacent ovarian tissue. However, this phenomenon does not appear to markedly affect ovarian function. Some effective biological mechanisms such as ferritin storage may effectively sequester free iron, so limiting its detrimental effects.