Selective peripheral tissue response to high testosterone levels in an infertile woman without virilization signs.

Summary: Total testosterone, which is peripherally converted to its biologically active form dihydrotestosterone (DHT), is the first-line hormone investigation in hyperandrogenic states and infertility in premenopausal women. Polycystic ovary syndrome (PCOS), the most common cause of hyperandrogenism and infertility in young women, is often associated with mild elevations of total testosterone. Whereas very high levels of total testosterone (>2-3 SD of normal reference), are most often associated with hyperandrogenic signs, menstrual irregularity, rapid onset of virilization, and demand a prompt investigation. Herein, we report a case of a 32-year-old woman who was referred to the endocrinology outpatient clinic due to secondary amenorrhea and extremely high testosterone levels without any virilization signs. We initially suspected pitfalls in the testosterone laboratory test. Total serum testosterone decreased after a diethyl-ether extraction procedure was done prior to the immunoassay, but testosterone levels were still elevated. An ovarian steroid-cell tumor (SCT) was then revealed, which was thereby resected. Twenty-four hours post surgery, the total testosterone level returned to normal, and a month later menstruation resumed. This case emphasizes that any discrepancy between laboratory tests and the clinical scenario deserves a rigorous evaluation to minimize misinterpretation and errors in diagnosis and therapeutic approach. Additionally, we describe a possible mechanism of disease: a selective peripheral target-tissue response to high testosterone levels that did not cause virilization but did suppress ovulation and menstruation. Learning points: Total testosterone is the most clinically relevant hormone in investigating hyperandrogenic states and infertility in premenopausal women. Very high total testosterone levels in women (>2-3 SD of normal reference) are most often associated with hyperandrogenic signs, menstrual irregularities, and a rapid onset of virilization. In women with very elevated testosterone levels and the absence of clinical manifestations, laboratory interference should be suspected, and diethyl ether extraction is a useful technique when other methods fail to detect it. Ovarian steroid cell tumors (SCT) encompass a rare subgroup of sex cord-stromal tumors and usually secrete androgen hormones. SCTs are clinically malignant in 25-43% of cases. A selective response of peripheral target tissues to testosterone levels, with clinical manifestations in some tissues and no expression in others, may reflect differences in the conformation of tumor-produced testosterone molecules.

Prediction of vaginal birth after one ceasarean delivery for non-progressive labor.

PURPOSE: A model exists that predicts the probability of vaginal birth after cesarean (VBAC). That model is not stratified by indication at first cesarean. The aim of the study was to identify factors that may predict successful VBAC in patients operated for arrest of dilatation or descent at their first cesarean. METHODS: Retrospective analysis of all women with trials of labor after one cesarean (TOLAC) for non-progressive labor between November 2008 and October 2015 was performed (n = 231). A multivariate logistic regression analysis was carried out to generate a prediction model for VBAC at hospital admission for planned TOLAC. RESULTS: During the study period, we had 231 parturient women who chose to undergo TOLAC following one previous cesarean delivery for non-progressive labor. Successful VBAC occurred in 155 (67.0%) parturient women. A model consisting of previous successful VBAC, lower head station on decision at previous cesarean delivery, lower newborn weight at previous cesarean delivery and larger cervical effacement on admission at delivery planned for TOLAC correctly classified 75.3% of cases (R 2 = 0.324, AUC 0.80, 95% CI 0.70-0.89, p < 0.001). CONCLUSION: A predictive model, which incorporates four variables available at hospital admission for the planned TOLAC, has been developed that allows the determination of likelihood of successful VBAC following one cesarean delivery for non-progressive labor.

Impact of quadrivalent human papillomavirus vaccine on genital warts in an opportunistic vaccination structure.

OBJECTIVE: Genital warts are the most common sexually transmitted disease and have a detrimental impact on quality of life. Genital warts could be prevented by prophylactic HPV vaccination. The objective was to study real-life benefit of opportunistic HPV vaccination on age and gender specific incidence of genital warts. METHODS: We performed a register-based population cohort study from publicly funded health-care provider in Israel. The incidence of genital warts was assessed during three time frame intervals: 2006-2008 (pre-vaccination effect period) 2009-2012 (early post-vaccination effect period) and 2013-2015 (late post-vaccination effect period), with an average annual number of members of 1,765,481, 1,906,774 and 2,042,678 in the years 2006-2008, 2009-2012 and 2013-2015, respectively. RESULTS: Among females, annual incidence of genital warts per 100,000 women decreased from 210.43 to 161.71 (OR 0.76, 95%CI 0.71-0.82, p<0.001) and to 146.8 (OR 0.69, 95%CI 0.66-0.72, p<0.001) between pre-vaccination period and early and late post-vaccination periods, respectively. Among males, annual incidence of genital warts per 100,000 men decreased from 262.85 to 232.40 (OR 0.88, 95%CI 0.83-0.93, p<0.001) and to 234.01 (OR 0.88, 95%CI 0.86-0.91, p<0.001) between pre-vaccination period and early and late post-vaccination periods, respectively. CONCLUSIONS: There is a potential benefit in reducing incidence of genital warts even in opportunistic HPV vaccination structure. This information may be relevant for health-care providers in countries where national immunization programs do not include HPV vaccines.

Was Queen Jane Seymour (1509-1537) Delivered by a Cesarean Section?

No direct evidence documents exactly how Jane Seymour gave birth on October 12, 1537. Several later commentators have raised cesarean birth as an option. This paper tries to establish the probable cause of Jane Seymour's death in accordance with present-day knowledge of obstetrics and whether or not a cesarean section could have been actually performed in sixteenth-century England. It appears almost certainly that there were no obstetrical indications that would have led the Queen's physicians to operate on her, a surgeon was not present at her delivery, cesarean section on a living woman was not regularly performed in England in 1537, puerperium events do not support surgery, and the existing pro-cesarean confirmation was politically motivated. Therefore, the most likely mode of Jane Seymour's delivery was vaginal rather than cesarean.

Reoccurrence of retained placenta at a subsequent delivery: an observational study.

OBJECTIVE: To test the generalizability of previously reported increased risk of reoccurrence of retained placenta in yet another setting. METHODS: In this observational retrospective study we longitudinally followed women who had a vaginal delivery complicated by a partial or complete retained placenta at Edith Wolfson Medical Center between 1 January 2009 and 31 December 2012. The study group included parturient women who had a partial or complete retained placenta after a vaginal delivery (n = 90). The control group included parturient women who did not have a partial or complete retained placenta after a vaginal delivery from the same time period using the same inclusion criteria (n = 90). RESULTS: Retained partial or complete placenta at a previous delivery was found to be an independent risk factor for retained partial or complete placenta in a subsequent delivery (adjusted OR 9.8, 95%CI 1.2 to 80.6, p = 0.032) and for retained partial or complete placenta and/or postpartum hemorrhage in a subsequent delivery (adjusted OR 14.1, 95% CI 1.7 to 111.9, p = 0.012), after controlling for gestational age and induction of labor at previous delivery. CONCLUSION: Retained partial or complete placenta at an index delivery increases the risk of reoccurrence of retained partial or complete placenta in a subsequent delivery.

The changing indications and rates of cesarean section in one academic center over a 16-year period (1997-2012).

OBJECTIVE: To compare trends and rates of cesarean section delivery by indication in one academic center. MATERIALS AND METHODS: A retrospective analysis of the indications of all cesarean sections performed in Edith Wolfson Medical Center, Holon, Israel, a tertiary healthcare university facility, during 1997-2012 was done. Each delivery was assigned to the primary indication noted for that pregnancy, regardless of other indications reported. Whenever more than one indication was present, the principle indication chosen by the attending obstetrician was chosen for the analysis. RESULTS: The cesarean section rate gradually rose from 15.29% in 1997 to 21.10% in 2012, with an overall cesarean section rate of 20.66%. The cesarean section rate between 1997 and 2000 was 17.52%, between 2001 and 2004 was 18.5%, between 2005 and 2009 was 22.86%, and between 2009 and 2012 was 22.07% (p < 0.001). The five leading primary indications across the years were previous cesarean section (26.0%), non-reassuring fetal heart rate pattern (18.1%), malpresentation (16.9%), labor dystocia (8.8%), and suspected macrosomia (7.2%). CONCLUSION: Previous cesarean section persistently increased and was the leading indication throughout the years. Any attempt to reverse this trend must be based on reduction of the primary cesarean section rate.

Caesarean section in Ancient Greek mythology.

The narrative of caesarean birth appears on several occasions in Greek mythology: in the birth of Dionysus is the God of the grape harvest and winemaking and wine; in the birth of Asclepius the God of medicine and healing; and in the birth of Adonis the God of beauty and desire. It is possible, however not obligatory, that it was not solely a fantasy but also reflected a contemporary medical practice.

The expression of heparanase in normal and preeclamptic placentas.

OBJECTIVE: Heparanase plays a central role in processes of placentation. Abnormal placentation may result in inadequate uteroplacental blood flow, leading to unsuccessful pregnancy outcome and preeclampsia. We aimed to evaluate heparanase expression in placentas of preeclamptic patients. MATERIALS AND METHODS: Placental tissue samples were collected immediately after delivery from 9 preeclamptic patients and 3 healthy controls at term, and were analyzed by immunohistochemistry, western blot analysis and real-time PCR, with regard to the presence of heparanase. RESULTS: Immunohistochemistry staining for heparanase did not differ between normal and preeclamptic placental sections. On the other hand, western blot analysis revealed increased expression of heparanase in preeclpamptic placentas compared to controls, p = 0.001. Similarly, RT-PCR analysis showed also an increased expression of heparanase m-RNA compared to health controls, p = 0.005. CONCLUSION: Heparanase is over expressed in preeclamptic placentas compared to normal healthy controls, suggesting its role in the development of preeclampsia.

Personality, fear of childbirth and birth outcomes in nulliparous women.

PURPOSE: This study was aimed at investigating the delivery continuum starting from constant personality variables and their association with Fear of childbirth (FOC) pre-partum, following the association of FOC pre-partum with the delivery process (as measured by birth outcome variables and subjective experience) and the effect of all of these variables over FOC post-partum. METHODS: In this prospective questionnaire study, 101 nulliparous, singleton pregnancy, healthy parturients were randomly recruited during 2011. Questionnaires were administered on admittance to the delivery ward (FOC, anxiety-sensitivity index, demographic information) and 2 days post-partum (FOC, Big five inventory and a question regarding the birth experience). Medical Variables were taken from medical records. RESULTS: FOC pre- and post-partum were associated with neuroticism (p < 0.05; p < 0.01) and anxiety sensitivity (p < 0.01). FOC pre-partum was correlated with mode of delivery, higher FOC pre-partum associated with instrumental delivery and emergency CS (p < 0.01). FOC post-partum was associated with both mode of delivery and length of the second phase of delivery (p < 0.05). Hierarchical regression analysis showed FOC pre-partum (ß = 0.35, p < 0.01), anxiety sensitivity (ß = 0.38, p < 0.01), mode of delivery (ß = 0.19, p < 0.05) and birth experience (ß = -0.17, p < 0.05) as major predictors for high FOC post-partum explaining 61 % of variance (F (7,84) = 16.82; p < 0.001). CONCLUSIONS: The difference between FOC levels pre- and post-partum was associated with personality variables and birth outcomes resulting in a model describing the variance in FOC post-partum by all of the above mentioned variables. As the implications of FOC over delivery outcomes are evident, women suffering from FOC pre-partum should be screened routinely before delivery and offered proper care.

Point prevalence of abnormal thyroid-stimulating hormone during the first trimester of pregnancy in Israel.

BACKGROUND: The prevalence of thyroid dysfunction in early pregnancy in Israel is not known. OBJECTIVES: To assess the rate of abnormal thyroid-stimulating hormone (TSH) tests in low risk pregnant women attending a community clinic in Israel. METHODS: We conducted a retrospective analysis of the charts of low risk pregnant women (n = 303) who had undergone a TSH screening during the first trimester of pregnancy at Clalit Health Services Women's Health Centers in Ashkelon and Tel Aviv. TSH of 0.1-2.5 mIU/L during the first trimester was considered to be normal. RESULTS: The TSH levels ranged from 0.04 to 13.3 mIU/L (median 1.73 mIU/L, mean 1.88 mIU/L).The rate of abnormal TSH was 25.6%, with low TSH 2.3% and high TSH 23.4%. The prevalence of abnormal TSH was not influenced by gravidity (primigravidas versus multigravidas) or place of residence (Ashkelon or Tel Aviv). CONCLUSIONS: In view of the high prevalence of abnormal TSH (25.6%) in pregnant women in Israel during the first trimester, a universal country-wide screening should be considered.

Comparison of maternal outcomes from primary cesarean section during the second compared with first stage of labor by indication for the operation.

OBJECTIVE: To compare maternal outcomes when cesarean sections were performed in the second stage of labor to those performed in the first stage of labor by indication for the operation. STUDY DESIGN: This is a retrospective cohort (n=383) of term parturient women who underwent primary cesarean section during active labor. Cases were drawn from the Obstetrics Department, E. Wolfson Medical Center, a tertiary health care university facility, during a 24 month period. All cases were term singleton pregnancies in vertex presentation following unremarkable pregnancy. Maternal morbidity was assessed. RESULTS: A significantly higher rate of unintentional uterine incision extensions was observed in cesarean sections performed during second stage compared to first stage (17.1% vs. 4.6%, p=0.001). It was higher whenever (at first or second stage) the fetal head was pushed (20.0% vs. 5.4%, p=0.0024). Unintentional uterine incision extensions were significantly more frequent when the cesarean section was performed for non-progressive labor during the second stage compared to first stage (16.1% vs. 3.6%, p=0.0052). Uterine atonia was more frequent among parturient women who underwent cesarean section for non-progressive labor during the first stage compared to second stage (16.7% vs. 4.8%, p=0.0382). CONCLUSION: Uterine atony during first stage cesarean section and unintentional uterine incision extensions during second stage cesarean section were significantly more frequent when the operation was performed for non-progressive labor.

Total and differential leukocyte count percentiles in healthy singleton term women during the first stage of labor.

AIMS: To establish leukocyte count and differential percentiles in healthy singleton term laboring women during spontaneous normal vaginal labor following an uncomplicated pregnancy. METHODS: An analysis of the records of all women (n = 762) who delivered at our delivery ward during a 2-month period was performed. After exclusion for cesarean delivery, induction of labor, pregnancy complications, preterm labor, multiple pregnancy, fever on admission, and lack of full blood count on admission, 365 parturient women during the 1st stage of labor were included in the final analysis. The total and differential leukocyte counts were determined by standard procedure by an automated cell counter. RESULTS: The leukocyte count range on admission to the delivery ward during the 1st stage of labor in healthy parturient women was between 4.4 × and 21.7 × 10(3)/µl and the 99th percentile limit was 20.06 × 10(3)/µl. The total leukocyte count was not influenced by cervical dilatation, ruptured membranes, or the presence and regularity of uterine contractions. CONCLUSION: An observed leukocyte count within the 99th percentile limit (20.06 × 10(3)/µl) in an otherwise normal parturient woman is reassuring in the absence of other clinical evidence.

Duration of labor by gestational week in nulliparous women.

OBJECTIVES: To assess whether labor length differs by week of gestation. METHODS: In this observational cross-sectional study, we compared duration of labor by gestational age (36 + 0 through 40 + 6 weeks) in primiparous singleton parturients with vertex presentation. Data were acquired for a period of 24 months (2010-2011). RESULTS: In general, the rate of change in cervical dilatation decreased as gestational week at delivery advanced: 1.8 ± 1.0 cm/h, 1.5 ± 0.9 cm/h, 1.3 ± 0.8 cm/h, 1.6 ± 1.5, and 1.3 ± 1.0 cm/h at 36th, 37th, 38th, 39th and 40th gestational week, respectively (p = 0.040). Concurrently, the total labor duration (1st + 2nd + 3rd stages) increased as gestational age advanced: 423.6 ± 180.9 min, 496.5 ± 212.6 min, 545.9 ± 247.1 min, 483.8 ± 256.3 min, and 568.2 ± 273.8 min at 36th, 37th, 38th, 39th and 40th gestational week, respectively (p = 0.013). CONCLUSIONS: Gestational week of pregnancy may alter the duration of labor, specifically, the length of labor increases as gestational week at delivery advances.

The effect of cigarette smoking during pregnancy on mode of delivery in uncomplicated term singleton pregnancies.

OBJECTIVE: To examine the influence of cigarette smoking during pregnancy on mode of delivery. METHODS: A retrospective analysis of 6105 uncomplicated term singleton pregnancies for mode of delivery was performed with respect to smoking status. RESULTS: Of all, 680 (84.0%) smokers and 4588 (86.7%) non-smokers had a spontaneous vaginal delivery, 65 (8.0%) smokers and 393 (7.4%) non-smokers had an instrumental delivery and 65 (8.0%) smokers and 314 (5.9%) non-smokers had a cesarean delivery (p = 0.051). Smoking during pregnancy increased the risk of any operative or instrumental intervention by OR 1.240, 95% CI 1.012-1.523. Non-reassuring fetal heart rate pattern that warranted either cesarean or instrumental intervention was present in 99 (12.2%) out of 810 smokers and in 392 out of 5295 (7.4%) non-smokers, p < 0.001). Smoking during pregnancy increased the risk of non-reassuring fetal heart rate pattern that warranted either cesarean or instrumental intervention by OR 1.650 (95% CI 1.341-2.022). CONCLUSION: Women with uncomplicated term singleton pregnancies who smoke during pregnancy are at an increased risk of fetal compromise during labor (as judged by non-reassuring fetal heart rate pattern), leading to increased rates of operative delivery (cesarean either instrumental).

Sexual function after childbirth by the mode of delivery: a prospective study.

PURPOSE: The objective of the present study was to evaluate sexual behavior longitudinally in the postpartum period by mode of delivery. METHODS: In this prospective study, five groups were defined: women who delivered vaginally without an episiotomy (n = 16), women who delivered vaginally with an episiotomy (n = 14), women who delivered by instrumental delivery (n = 16), women who delivered by an emergent cesarean section (n = 19), and women who delivered by an elective cesarean section (n = 17). Sexual behavior was assessed by the female sexual function index (FSFI) questionnaire at 6, 12, and 24 weeks postpartum and by the timing of resumption of sexual intercourse. RESULTS: The mean ± SD self-reported timing of resumption of sexual activity was 4.5 ± 1.8, 7.9 ± 3.0, 7.3 ± 3.4, 6.1 ± 2.6, and 6.1 ± 2.4 weeks in the vaginal delivery without an episiotomy group, in the vaginal delivery with an episiotomy group, in the instrumental delivery group, in the elective cesarean delivery group, and in the emergent cesarean delivery group, respectively (p = 0.013). The FSFI total score in the entire study group (n = 82) was 14.1 ± 10.8, 24.6 ± 7.6, and 27.7 ± 5.1 at 6, 12, and 24 weeks postpartum, respectively (p < 0.05). The FSFI total score did not differ significantly across types of mode of delivery at 6, 12, or 24 weeks postpartum. CONCLUSION: The significance by delivery mode difference in the postpartum resumption of sexual activity was not accompanied by difference in sexual function scores. Specifically, elective cesarean delivery was not associated with a protective effect on sexual function after childbirth.

Need for episiotomy in a subsequent delivery following previous delivery with episiotomy.

PURPOSE: To assess the need of episiotomy in a subsequent delivery in women with previous primiparous vaginal delivery with episiotomy. METHODS: In this historical prospective study, we followed primiparous women who had an episiotomy at a normal vaginal delivery. The study group included parturient women (n = 201) who underwent an episiotomy at a vaginal delivery during a 2-year period (2001-2002). Inclusion criteria were: primiparity, term singleton vaginal delivery, episiotomy, and a subsequent vaginal delivery in Edith Wolfson Medical Center. Exclusion criteria were instrumental delivery at the index delivery, preterm delivery or twins at the subsequent delivery. Episiotomy in the enrolled parturient women was done when it is thought that failure to perform episiotomy would result in perineal tears. The control group (n = 201) was formed from the same time period and included women who had a spontaneous vaginal delivery without episiotomy. RESULTS: Of the 201 women with episiotomy at the index delivery, 48 (23.9 %) had episiotomy at the subsequent delivery compared to only 20 women (10.0 %) out of the 201 women without an episiotomy at index delivery (p < 0.05). Having an episiotomy at the index delivery significantly increased odds of a subsequent episiotomy (OR 2.84, 95 % CI 1.62-4.99, p < 0.05) and the risk of spontaneous perineal tears (59.2 vs. 23.4 %, p < 0.05) at the subsequent delivery. CONCLUSION: Episiotomy at first vaginal delivery significantly and independently increased the risk of repeated episiotomy and spontaneous perineal tears in a subsequent delivery.

Effects of an extended free-of-fee strategy on the rate of cervical Papanicolaou smear screening in Israel.

OBJECTIVE: To investigate the influence of an extended free-of-fee strategy on the rate of cervical Papanicolaou (Pap) smear screening in Israel. METHODS: A retrospective analysis was conducted of data obtained from a computer-generated list of women aged 15-74 years who attended appointments with Clalit Health Services between January 1, 2008, and November 30, 2011, during which Pap smears were taken. The basic strategy allowed a no-fee Pap smear once every 3 years between the ages of 35 and 54 years; the extended strategy allowed a no-fee Pap smear once every 3 years between the ages of 25 and 54 years. RESULTS: In all, 65 565 Pap smears were taken. The mean monthly study population was 161 438 women. The mean monthly Pap smear rate for the basic strategy was 0.64% ± 0.5% (95% confidence interval [CI], 0.59-0.68) versus 0.75% ± 0.6% (95% CI, 0.70-0.79) for the extended strategy (P=0.004). Age group (P<0.001), Pap smear strategy type (P<0.001), and combined age group and strategy type (P=0.028) each predicted the monthly rate of Pap smear screening in a univariate analysis. CONCLUSION: Implementation of the extended free-of-fee strategy increased the rate of Pap smear screening among Israeli women.

Mode of delivery in a subsequent pregnancy following previous instrumental delivery.

OBJECTIVE: To assess mode of subsequent delivery in women with previous instrumental vaginal delivery. STUDY DESIGN: In this retrospective longitudinal study we followed women who underwent instrumental delivery. The study group included all consecutive parturient women who underwent an instrumental vaginal delivery during a 24-month period (1996-1999). We then identified women who had a subsequent delivery in our center until the end of the year 2010. The control group included women who had a spontaneous vaginal delivery from the same time. RESULTS: During the index period we had 349 consecutive successful instrumental vaginal deliveries. Of those, 125 women had a subsequent delivery in our center (35.8%). In subsequent pregnancies, the spontaneous vaginal delivery rate was 76.8% and 90.4%; the instrumental delivery rate was 8.8% and 1.6%; and the cesarean rate was 14.4% and 8.0%, in the instrumental delivery, and spontaneous vaginal delivery groups, respectively (P<0.05). The odds ratio for a woman to undergo either an instrumental delivery or a cesarean after having an instrumental delivery in a previous pregnancy was 2.8 (95% confidence interval 1.4-5.9, P<0.05). CONCLUSION: Women with a previous instrumental delivery are at an increased risk of requiring either an instrumental delivery or a cesarean section in a subsequent pregnancy compared with women with a previous spontaneous vaginal delivery.