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Hormonal contraceptives are an effective and safe method for preventing pregnancy. Progestins used in contraception are either components of combined hormonal contraceptives (tablets, patches or vaginal rings) or are used as a single active ingredient in progestin mono-preparations (the progestin-only pill (POP), implants, intrauterine systems or depot preparations). Progestins are highly effective in long-term contraception when used properly, and have a very good safety profile with very few contraindications. A new oestrogen-free ovulation inhibitor (POP) has recently been authorised in the USA and the EU. This progestin mono-preparation contains 4 mg of drospirenone (DRSP), which has anti-gonadotropic, anti-mineralocorticoidic and anti-androgenic properties. The hormone administration regimen of 24 days followed by a 4-day hormone-free period was chosen to improve bleeding control and to maintain oestradiol concentrations at early follicular-phase levels, preventing oestrogen deficiency. Clinical trials have demonstrated a high contraceptive effectiveness, a very low risk of cardiovascular side effects and a favourable menstrual bleeding pattern. Due to the long half-life of DRSP (30 - 34 hours), the effectiveness of the preparation is maintained even if a woman forgets to take a pill on a single occasion. Studies involving deliberate 24-hour delays in taking a pill have demonstrated that ovulation inhibition is maintained if a single pill is missed. Following a summary of the current status of oestrogen-free contraception, this review article will describe the clinical development programme of the 4 mg DRSP mono-preparation and the resulting data on the effectiveness and safety of this new oestrogen-free oral hormonal contraceptive., Competing Interests: Conflict of Interest/Interessenkonflikt Pedro-Antonio Regidor is an employee of Exeltis./Pedro-Antonio Regidor ist Angestellter von Exeltis., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objectives: The Contraceptive Counselling (COCO) study tested whether a structured approach to assessing patient needs and expectations improved method choice and satisfaction with the contraceptive decision-making process., Methods: Physicians and women were invited to complete needs-based contraceptive counselling sessions using a structured questionnaire. Physicians recorded the individual responses online; women evaluated the process using an immediate post-consultation questionnaire and then via a structured online interview 6 months later., Results: A total of 92 gynaecologists and 1176 women participated: 951 women completed the immediate post-consultation survey and 145 took part in the 6 month online evaluation. There was a substantial increase in satisfaction with the current contraceptive method: the number of women reporting they were 'very satisfied' with their contraceptive method increased by 30%. This applied to starters and switchers as well as to women continuing with their previous method. Women were highly satisfied with the structured approach; 95% rated the counselling as 'good' or 'very good' and 'comprehensive and detailed'., Conclusion: Using a structured approach to share information tailored to women's needs can help them choose from a broader range of methods and, in some cases, change to a method more suitable to their individual needs, and ultimately increase satisfaction with their choice.

Aims This is an official interdisciplinary guideline published and coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The guideline was developed for use in German-speaking regions and is backed by numerous professional societies and organizations. The aim of this guideline is to provide an evidence- and consensus-based overview of the diagnostic approach and the management of hormonal contraception based on a systematic evaluation of the relevant literature. Methods To compile this S3-guideline, a systematic search for evidence was carried out in PubMed and the Cochrane Library to adapt existing guidelines and identify relevant reviews and meta-analyses. A structured evaluation of the evidence was subsequently carried out on behalf of the Guidelines Commission of the DGGG, and a structured consensus was achieved based on consensus conferences attended by representative members from the different specialist societies and professions. Recommendations Evidence-based recommendations about the advice given to women requesting contraception were compiled. The guideline particularly focuses on prescribing contraceptives which are appropriate to women's individual needs, take account of her personal circumstances, and have few or no side effects., Competing Interests: Conflict of Interest/Interessenkonflikt The authorsʼ conflicts of interest are listed in the long version of the guideline./Die Interessenkonflikte der Autoren sind in der Langfassung der Leitlinie aufgelistet., (Thieme. All rights reserved.)

Background: Data on adrenarche and pubarche in girls with Turner syndrome (TS) are inconsistent in the literature., Methods: The cohort consisted of 94 girls and young women with TS born between 1971 and 2001 (age range: 3.1-23.2 yrs.), who were treated with human growth hormone and regularly presented at our outpatient clinic every 4 to 6 months.The longitudinal data of all patients were ascertained retrospectively from patient charts. The data collection ended in January 2016. Adrenarche was assessed by serum DHEAS levels and pubertal status by Tanner stages. Pubarche was defined as the appearance of pubic hair (PH2), whereas spontaneous puberty was defined as Tanner stage B2. The patients were retrospectively subdivided in two groups with regard to pubertal development: group 1 (n = 21) with spontaneous puberty and group 2 (n = 70) with induced puberty. Since blood samples were not taken at every visit, we generated seven groups according to the age of the children at which the blood samples were taken: 3-5, 5-7, 7-9, 9-11, 11-13, 13-15, and 15-17 yrs. Serum DHEAS and follicle-stimulating hormone (FSH) levels were measured by chemiluminescence immunoassay and compared with those of a control group of healthy girls., Results: Adrenarche started in TS girls between 5 and 7 years. TS girls had higher DHEAS levels than the control group, with statistically significant differences in the age groups 7 to 17 years. No differences were determined between the TS girls with spontaneous puberty and those with POI. TS girls in group 2 reached the Tanner stages PH2 (p < 0.04), PH3 (p < 0.01), PH4 and PH5 (p < 0.001) markedly later than TS girls in group 1., Conclusions: The onset of adrenarche in girls with TS undergoing GH therapy does not differ from that in healthy girls. However, adrenarche is more pronounced in girls with TS. There is no difference in DHEAS levels between the TS girls with spontaneous puberty and the TS girls with primary ovarian insufficiency (POI), while the tempo of pubarche is markedly slower in the girls with POI.

Introduction: Endometriosis is associated with hyperperistalsis and dysperistalsis in the uterus, and it has been shown that progesterone leads to a decrease in uterine contractility. The synthetic gestagen dienogest is often administered in women who are receiving conservative treatment for endometriosis, and it may be the treatment of choice. The present study investigated the effects of dienogest on uterine contractility in comparison with the known inhibitory effect of progesterone., Material and Methods: Eighty swine uteri were examined using an established extracorporeal perfusion model. The uteri were perfused for at least 4 hours with progesterone, dienogest, or a modified Krebs-Ringer solution as the control group, with uterine contractions being measured using an intrauterine microchip catheter. The amplitude and frequency of contractions and the area under the curve (AUC), reflecting overall contractility, were measured at two separate locations (the isthmus and fundus)., Results: Progesterone led to a significant decrease in the amplitude of uterine contractions and to reduced overall pressure (AUC) at the isthmus and fundus. Dienogest led to a significant decrease in the amplitude of contractions and overall pressure (AUC) in the area of the isthmus, but the decrease near the fundus was not significant. The frequency of uterine contractions was not influenced by either progesterone or dienogest., Conclusions: These results confirm the known inhibitory effect of progesterone on uterine contractility (relative to amplitude of contractions and overall contractility), affecting the whole organ. Perfusion of the uterus with dienogest also led to a general decrease in uterine contractility similar to the effect of progesterone., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction Would adolescent girls in Germany choose a different method of contraception to the combined oral contraceptive if provided with the appropriate information? Is there a need for long-acting contraception among our adolescent girls? How satisfied are female patients with the information they receive at their respective gynaecology practices, and how much do the girls know about different methods of contraception? Materials and Methods In the study "Thinking About Needs in COntraception" (TANCO), not only female patients, but also their respective gynaecologists were surveyed online about current methods of contraception, their satisfaction with these methods, and also their level of knowledge concerning the individual methods of contraception, the situation related to advice about different contraceptive options and their general satisfaction with gynaecological care. This article presents the data from the subset of adolescent girls aged 14 to 19 years (n = 2699) out of the total of 18 521 women surveyed. Results The girls surveyed were familiar with at least the name of more than five different methods of contraception (average 5.3). The doctors assumed that the respondents would know only 4.2 different methods. When asked explicitly about how the individual methods of contraception work, clear deficits became evident. This applies not only to the entire population of respondents, but also the users of the respective contraceptive method. In addition, a strong interest in long-acting contraception emerged from the survey, particularly among young women. Discussion The data from the TANCO study reveal a clear discrepancy between the existing contraception almost exclusively in the form of the contraceptive pill and the contraceptive options considered by adolescent girls if they are thoroughly informed. The need for education into alternatives to the pill is high, as is the willingness to use such alternatives after receiving information - much higher than the figures suggested by the gynaecologists.

Aim: The aim of this official guideline published by the German Society of Gynecology and Obstetrics (DGGG) and coordinated with the German Society of Urology (DGU) and the German Society of Reproductive Medicine (DGRM) is to provide consensus-based recommendations, obtained by evaluating the relevant literature, on counseling and fertility preservation for prepubertal girls and boys as well as patients of reproductive age. Statements and recommendations for girls and women are presented below. Statements or recommendations for boys and men are not the focus of this guideline., Methods: This S2k guideline was developed at the suggestion of the guideline commission of the DGGG, DGU and DGRM and represents the structured consensus of representative members from various professional associations (n = 40)., Recommendations: The guideline provides recommendations on counseling and fertility preservation for women and girls which take account of the patient's personal circumstances, the planned oncologic therapy and the individual risk profile as well as the preferred approach for selected tumor entities.

Background: Daysy is a fertility monitor that uses the fertility awareness method by tracking and analyzing the individual menstrual cycle. In addition, Daysy can be connected to the application DaysyView to transfer stored personal data from Daysy to a smartphone or tablet (IOS, Android). This combination is interesting because as it is shown in various studies, the use of apps is increasing patients´ focus on their disease or their health behavior. The aim of this study was to investigate if by the additional use of an App and thereby improved usability of the medical device, it is possible to enhance the typical-use related as well as the method-related pregnancy rates., Result: In the resultant group of 125 women (2076 cycles in total), 2 women indicated that they had been unintentionally pregnant during the use of the device, giving a typical-use related Pearl-Index of 1.3. Counting only the pregnancies which occurred as a result of unprotected intercourse during the infertile (green) phase, we found 1 pregnancy, giving a method-related Pearl-Index of 0.6. Calculating the pregnancy rate resulting from continuous use and unprotected intercourse exclusively on green days, gives a perfect-use Pearl-Index of 0.8., Conclusion: It seems that combining a specific biosensor-embedded device (Daysy), which gives the method a very high repeatable accuracy, and a mobile application (DaysyView) which leads to higher user engagement, results in higher overall usability of the method.

Purpose: The aim of this study was to determine the extent to which women's choice of contraceptive method depends on the advice received from their gynecologist and whether more intensive counseling might lead to more frequent use of long-acting reversible contraception (LARC)., Methods: A total of 1089 physicians and 18,521 women responded to 32 or 37 questions, respectively, using an online questionnaire. The women were asked about their current use of contraceptive methods, the extent of their satisfaction with them, their satisfaction with the counseling they had received, and whether they wanted to have more information about contraception. The physicians were similarly asked which contraceptive methods were being used, how satisfied with them they were, how they would assess their patients' satisfaction with them, and whether the women wanted to have more information., Result: The results showed that 61% of the women were using oral contraceptives, and a total of only 9% were using behavior-independent long-term contraceptive methods. However, 60% of the women stated that long-term contraception would be an option for them if they had more information about it. Gynecologists underestimated this figure, at only 18%. Whereas 66% of the gynecologists believed that their patients never forgot to take the pill, nearly, half of the women stated that they had forgotten it at least once during the previous 3 months., Conclusion: The small number of women who use long-term contraception is in clear contrast to the fact that many women want to have a very safe but also behavior-independent method.

Patients with the Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) have a congenital utero-vaginal cervical aplasia, but normal or hypoplastic adnexa and develop with normal female phenotype. Some reports mostly demonstrated regular steroid hormone levels in small MRKH cohorts including single MRKH patients with hyperandrogenemia and a clinical presentationof hirsutism and acne has also been shown. Genetically a correlation of WNT4 mutations with singular MRKH patients and hyperandrogenemia was noted. This study analyzed the hormone status of 215 MRKH patients by determining the levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, 17-OH progesterone, testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and prolactin to determine the incidence of hyperandrogenemia and hyperprolactinemia in MRKH patients. Additional calculations and a ratio of free androgen index and biologically active testosterone revealed a hyperandrogenemia rate of 48.3%, hyperprolactinemia of 9.8% and combined hyperandrogenemia and hyperprolactinemia of 4.2% in MRKH patients. The rates of hirsutism, acne and especially polycystic ovary syndrome (PCOS) were in the normal range of the population and showed no correlation with hyperandrogenemia. A weekly hormone assessment over 30 days comparing 5 controls and 7 MRKH patients revealed high androgen and prolactin, but lower LH/FSH and SHBG levels with MRKH patients. The sequencing of WNT4 , WNT5A , WNT7A and WNT9B demonstrated no significant mutations correlating with hyperandrogenemia. Taken together, this study shows that over 52% of MRKH patients have hyperandrogenemia without clinical presentation and 14% hyperprolactinemia, which appeals for general hormone assessment and adjustments of MRKH patients., (© 2017 Society for Reproduction and Fertility.)

Purpose: Extracting ovarian tissue before oncologic therapy and transplanting it afterwards are increasingly being used to preserve fertility in women. This study describes standardized and safe operative procedures, with few complications, and reports the resulting ovarian function and pregnancy rates., Methods: The standardized operative techniques for removing and transplanting ovarian tissue used at the Erlangen center are: for tissue removal, one-third to half of the tissue from one ovary is excised with scissors, without tissue coagulation; for subsequent transplantation, pieces of ovarian tissue are placed in a retroperitoneal pocket without closure of the pocket., Results: Between January 2007 and December 2015, ovarian tissue was extracted in 399 women and transplanted following cancer therapy in 38. No surgical complications were observed within 28 days. To date, there have been ten pregnancies and nine live births after transplantation in seven different women; 26 of the 38 women developed hormonal activity, confirmed by a menstrual cycle or raised serum estradiol levels., Conclusions: The techniques for laparoscopic removal and transplantation of ovarian tissue described here provide a standardized method with a very low risk of complications. The pregnancy rate after ovarian tissue transplantation, currently 15-30%, can be expected to rise further in the near future.

Purpose: This guideline of the German Society of Pediatric Endocrinology and Diabetology (DGKED) is designed to be experts' opinion on the current concept of prenatal therapy for congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH). Several scientific medical societies have also participated in the guideline. It aims to offer guidance to physicians when they counsel affected families about prenatal therapy. Methods: The experts commissioned by the medical societies developed a consensus in an informal process. The consensus was subsequently confirmed by the steering committees of the respective medical societies. Recommendations: Prenatal CAH therapy is an experimental therapy. We recommend designing and using standardized protocols for the prenatal diagnosis, therapy and long-term follow-up of women and children treated prenatally with dexamethasone. If long-term follow-up is not possible, then prenatal therapy should not be performed.

Background/aim: Uterine quiescence at the time of embryo transfer is a prerequisite for successful in vitro fertilization (IVF). This study assessed whether prostaglandin-induced contractions in the perfused swine uterus can be reduced by progesterone., Materials and Methods: Fifty-eight non-pregnant swine uteri were perfused using an established extracorporeal perfusion model. Intrauterine pressure changes during perfusion with prostaglandin (PG) administration (PGE1, PGE2, PGF2α) and progesterone (1 pg/ml, 10 pg/ml, 25 pg/ml, 50 pg/ml) were assessed using an intrauterine double-chip microcatheter., Results: The contraction-stimulating effect of PGs was clearly reduced by progesterone. Only PGE1 still triggered relevant contractions during continuous perfusion with progesterone solution, up to a concentration of 10 pg/ml. With PGE2 and PGF2α, a clear reduction of uterine contractility was observed even at at a progesterone concentration of 1 pg/ml., Conclusion: The extracorporal perfusion model of swine uteri shows that PG-induced contractions can be reduced in a dose-dependent manner by progesterone., (Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Congenital genital malformations occurring in the female population are estimated to be 5 per 1000 and associate with infertility, abortion, stillbirth, preterm delivery and other organ abnormalities. Complete aplasia of the uterus, cervix and upper vagina (Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome) has an incidence of 1 per 4000 female live births. The molecular etiology of congenital genital malformations including MRKH is unknown up to date. The homeobox (HOX) genes HOXA10 and HOXA13 are involved in the development of human genitalia. In this investigation, HOXA10 and HOXA13 genes of 20 patients with the MRKH syndrome, 7 non-MRKH patients with genital malformations and 53 control women were sequenced to assess for DNA variations. A total of 14 DNA sequence variations (10 novel and 4 known) within exonic and untranslated regions were detected in HOXA10 and HOXA13 among our cohorts. Four HOXA10 and two HOXA13 DNA sequence variations were found solely in patients with genital malformations. In addition to mutations resulting in synonymous amino acid substitutions, in the HOXA10 gene a missense mutation was identified and predicted by computer analysis as probably damaging to protein function in two non-MRKH patients, one with a bicornate and the other patient with a septated uterus. A novel exonic HOXA10 cytosine deletion was also identified in a non-MRKH patient with a septate uterus and renal malformations resulting in a premature stop codon and loss of the homeodomain helix 3/4. This cytosine deletion and the missense mutation in HOXA10 were analysed by real time PCR and sequencing, respectively, in two additional larger cohorts of 103 patients with MRKH and 109 non-MRKH patients with genital malformations. No other patients were found with the cytosine deletion however one additional patient was identified regarding the missense mutation. Rare DNA sequence variations in the HOXA10 gene could contribute to the misdevelopment of female internal genitalia., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: The aim of this retrospective study was to describe the spectrum of genital and associated malformations in women with Mayer-Rokitansky-Küster-Hauser syndrome using evaluated diagnostic procedures and the Vagina Cervix Uterus Adnex - associated Malformation classification system (VCUAM)., Methods: 290 women with MRKH syndrome were clinically evaluated with using clinical examinations, abdominal and perineal/rectal ultrasound, MRI, and laparoscopy., Results: Classification of female genital malformation according to the Vagina Cervix Uterus Adnex - associated Malformation classification system was possible in 284 women (97.9%). Complete atresia of Vagina (V5b) and bilateral atresia of Cervix (C2b) were found in 284 patients (100%). Uterus: bilateral rudimentary or a plastic uterine horns were found in 239 women (84.2%). Adnexa: normal Adnexa were found in 248 women (87.3%). Malformations: associated malformations were found in 126 of 282 evaluable women (44.7%), 84 women (29.6%) had malformations of the renal system. Of 284 women with Mayer-Rokitansky-Küster-Hauser syndrome 212 women (74.7%) could be classified as V5bC2bU4bA0. The most frequent classification was V5bC2bU4bA0M0 (46.8%) diagnosed in 133 of 284 women., Conclusions: Complete atresia of vagina and cervix were found in all patients, variable malformations were found with uterus and adnexa. A variety of associated malformations were present, predominantly of the renal system. It is therefore recommended that all patients with genital malformations should be evaluated for renal abnormalities.

The active transport of sperm through the female genital tract is a very important factor in the fertilisation process. There is conflicting evidence as to whether seminal plasma has a positive or a negative effect on reproductive performance regarding the sperm transport in the female genital tract. In this study, we investigated if the perfused swine uterus is an appropriate model to study the effect of human seminal plasma on uterine contractility. It was found that repeated application of human seminal plasma caused a significantly higher rise in pressure and frequency of contractions in perfused swine uteri compared to buffer [a 1.8-fold and 1.5-fold pressure rise (Δt1SP, P = 0.025; Δt2SP, P = 0.004)] after the first and second application of seminal plasma respectively, and even a 2-fold pressure rise after the third application with a statistical significance of P = 0.007. The pressure rise caused by the seminal plasma over the entire period of application was calculated using a mathematical programme and was represented by the integral of the pressure curve over time. This perfusion model as well as the use of pressure-time integrals is suitable for patho-physiological studies of the uterus., (© 2011 Blackwell Verlag GmbH.)

Background/aim: Obtaining human embryonic stem cell lines has so far involved destroying the embryos. This has given rise to ethical concerns and is not permitted in most countries. This investigation tested whether removing multiple cells from blastocysts might allow continued embryonic development., Materials and Methods: A total of 40 blastocysts from a black mouse strain were biopsied. The mouse blastocysts were fixed with a holding pipette. The zona pellucida and trophectoderm layer were penetrated with an injection pipette, and cells from the inner cell mass (ICM) were aspirated. The pipette was removed and the ICM cells were transferred into a medium., Results: The blastocysts collapsed after pipette removal and were allowed to regenerate for 6 h. Twenty-four blastocysts recovered, expanded and were implanted into four white surrogate mothers. One surrogate mother gave birth to two black pups., Conclusion: This experiment demonstrates that nondestructive blastocyst biopsy from the ICM is possible in mice.

Background: According to the classification of polycystic ovary syndrome (PCOS) published by the Androgen Excess Society (AES), 10 different phenotypes of the condition are possible. The question remains of whether using these phenotypes might enable us to identify women with impaired insulin resistance or an impaired lipid profile among patients with PCOS., Materials and Methods: A prospective cohort analysis was performed of 313 women with diagnosed PCOS and 80 control individuals. The screening panel included a physical examination, weight and height measurement, ultrasonography of the ovaries, and hormone, glucose, lipid, and insulin resistance measurements., Results: There were no statistically significant differences in insulin resistance parameters between the different phenotypes. There were no statistically significant differences in body mass index (BMI) in any of the groups, but BMI showed the best correlation with insulin resistance in all women with PCOS and controls. Sex hormone-binding globulin (SHBG) was inversely correlated with insulin resistance in women with PCOS and controls. High-density lipoprotein (HDL) was negatively correlated with insulin resistance, and free testosterone was positively correlated with it, only in women with PCOS., Conclusions: Using the different phenotypes described in the AES classification shows no advantages for identifying women with aggravated insulin resistance or impaired lipid profile among patients with PCOS., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To compare different diagnostic procedures for staging malformations associated with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome., Design: Retrospective two-center cohort study (Canadian Task Force classification II-2)., Setting: University hospital., Patient(s): One hundred and thirty-eight women with MRKH., Intervention(s): Clinical examinations, abdominal or perineal/rectal ultrasound, magnetic resonance imaging (MRI), and laparoscopy., Main Outcome Measure(s): Agreement between the results obtained with the other methods and the results obtained with the reference methods for correct staging of malformations, presented as kappa values (κ)., Result(s): The VCUAM (vagina cervix uterus adnex-associated malformation) classification system was used to classify genital malformations in 138 women with MRKH. The reference methods for examining the individual organs were: vagina-clinical examination; cervix/uterus and adnexa-laparoscopy; and urinary tract malformations-MRI. The values obtained were as follows. Vagina was κ 0.74 for MRI versus clinical examination; ultrasound and laparoscopy did not allow adequate description of vaginal malformations. Cervical findings were rarely detailed with any of the imaging methods. Uterus was κ 0.93 for MRI versus laparoscopy, and κ 0.83 for ultrasound. For adnexa, only laparoscopy was able to describe the morphology adequately. The urinary tract was κ 0.87 for ultrasound versus MRI., Conclusion(s): For the correct staging of malformations associated with MRKH, MRI or a combination of clinical examination and ultrasound are equivalent. However, none of the imaging methods adequately describes adnexal morphology., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Thyroid disorders have a great impact on fertility in both sexes. Hyperthyroidism and hypothyroidism cause changes in sex hormone-binding globulin (SHBG), prolactin, gonadotropin-releasing hormone, and sex steroid serum levels. In females, thyroid hormones may also have a direct effect on oocytes, because it is known that specific binding sites for thyroxin are found on mouse and human oocytes. There is also an association between thyroid dysfunction in women and morbidity and outcome in pregnancy. In males, hyperthyroidism causes a reduction in sperm motility. The numbers of morphologically abnormal sperm are increased by hypothyroidism. When euthyroidism is restored, both abnormalities improve or normalize. In women, the alterations in fertility caused by thyroid disorders are more complex. Hyper- and hypothyroidism are the main thyroid diseases that have an adverse effect on female reproduction and cause menstrual disturbances--mainly hypomenorrhea and polymenorrhea in hyperthyroidism, and oligomenorrhea in hypothyroidism. In recent studies, it has become evident that it is not only changes in serum levels of SHBG and sex steroids that are responsible for these disorders, but also alterations in the metabolic pathway. Adequate levels of circulating thyroid hormones are of primary importance for normal reproductive function. This review presents an overview of the impact of thyroid disorders on reproduction., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To identify genetic causes of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome., Design: Prospective laboratory study., Setting: University hospital., Patient(s): Fifty-six patients with MRKH syndrome., Intervention(s): Identification of microdeletions and -duplications in a group of 48 MRKH patients by array-CGH. Results obtained by array-CGH were confirmed by RT-qPCR. Sequential analysis of two candidate genes LHX1 and HNF1B in a group of 56 MRKH patients., Main Outcome Measure(s): Identification of chromosomal regions and genes (recurrent and private) associated with MRKH syndrome., Result(s): We could delineate three definitively relevant regions (1q21.1, 17q12, and 22q11.21) and suggest that LHX1 und HNF1B are candidate genes for MRKH syndrome, because we identified recurrent deletions affecting these genes and a possible causative missense mutation in LHX1., Conclusion(s): Our findings suggest that different chromosomal regions are associated with MRKH syndrome., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Congenital malformations involving the Müllerian ducts are observed in around 5% of infertile women. Complete aplasia of the uterus, cervix, and upper vagina, also termed Müllerian aplasia or Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, occurs with an incidence of around 1 in 4500 female births, and occurs in both isolated and syndromic forms. Previous reports have suggested that a proportion of cases, especially syndromic cases, are caused by variation in copy number at different genomic loci., Methods: In order to obtain an overview of the contribution of copy number variation to both isolated and syndromic forms of Müllerian aplasia, copy number assays were performed in a series of 63 cases, of which 25 were syndromic and 38 isolated., Results: A high incidence (9/63, 14%) of recurrent copy number variants in this cohort is reported here. These comprised four cases of microdeletion at 16p11.2, an autism susceptibility locus not previously associated with Müllerian aplasia, four cases of microdeletion at 17q12, and one case of a distal 22q11.2 microdeletion. Microdeletions at 16p11.2 and 17q12 were found in 4/38 (10.5%) cases with isolated Müllerian aplasia, and at 16p11.2, 17q12 and 22q11.2 (distal) in 5/25 cases (20%) with syndromic Müllerian aplasia., Conclusion: The finding of microdeletion at 16p11.2 in 2/38 (5%) of isolated and 2/25 (8%) of syndromic cases suggests a significant contribution of this copy number variant alone to the pathogenesis of Müllerian aplasia. Overall, the high incidence of recurrent copy number variants in all forms of Müllerian aplasia has implications for the understanding of the aetiopathogenesis of the condition, and for genetic counselling in families affected by it.

Objective: In transsexual people, cross-sex hormone therapy is an important component of medical treatment and results in a complete change in the sex hormone environment. Steroid hormones plays an important role in developing and maintaining bone mass and body composition in both sexes. The aim of this study was to evaluate changes in body composition and bone mineral density (BMD) during cross-sex hormone therapy in transsexuals using gonadotrophin-releasing hormone agonists and intramuscular oestrogens., Methods: 84 male-to-female transsexuals (MtFs) were treated with 10 mg oestradiol-17β valerate every 10 days. The study population was treated with subcutaneous injections of 3.8 mg goserelin acetate every 4 weeks to suppress endogenous sex hormone secretion completely. Endocrine parameters, body composition and BMD after 12 months and after 24 months were compared with baseline values., Results: There was a significant decline in gonadotrophins and testosterone, while oestradiol, sex hormone-binding globulin, and high-density lipoprotein levels increased significantly after 12 and 24 months. There was a significant increase in body mass index (BMI), fat mass, and lumbar spine bone mineral density in MtFs during the study period, while lean mass decreased significantly and no effect was observed on femoral bone mineral density., Conclusion: There was an increase in BMI associated with a shift from lean mass to fat mass. There appears to be no risk of osteoporosis developing in MtFs when there is adequate oestrogen substitution, even in the absence of testosterone. Furthermore in comparison with hormone regimes using oral medications, the complication rates appear to be lower in patients receiving gonadotrophin-releasing hormone agonists and intramuscular oestrogens., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To evaluate the impact of testosterone (T) administration to female-to-male transsexuals (FtMs) on insulin resistance and lipid parameters and to compare the effects with women with polycystic ovary syndrome (PCOS)., Design: Cohort analysis., Setting: University hospital., Patient(s): Twenty-nine FtMs and 240 women with PCOS., Intervention(s): Screening panel, ultrasound of the ovaries, hormone, lipid, and glucose and insulin measurements., Main Outcome Measure(s): Endocrine, metabolic parameters, and insulin resistance., Result(s): The PCOS women had significantly higher fasting, 1-h, and 2-h insulin levels and a significantly lower insulin sensitivity index compared with FtMs before and after their T treatment. There were higher triglyceride levels and lower high-density lipoprotein cholesterol levels upon T treatment in FtMs compared with the PCOS women. Women with PCOS had higher body mass index (BMI) values. Positive correlations between insulin resistance indices and BMI were found only in women with PCOS., Conclusion(s): Testosterone administration by itself showed little detrimental influence on insulin resistance indices, but it had significant effects on lipid profiles. Compared with T, BMI had a greater impact on insulin resistance in women with PCOS., (Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to evaluate long-term changes in endocrine and metabolic parameters and body mass index in women with polycystic ovary syndrome (PCOS) who were treated with metformin over 2 years without caloric restriction., Material and Methods: Twenty-six obese women with PCOS were treated with metformin over 2 years without caloric restriction. Clinical, metabolic and endocrine parameters and the body mass index were measured and an oral glucose tolerance test was carried out to calculate insulin resistance indices at the beginning and at the follow-up after 2 years. The Homeostatic Model for Assessment of Insulin Resistance (HOMA-IR) was calculated., Results: No significant changes in body mass index or HOMA-IR were observed. However, a significant decrease in fasting and 2-h insulin levels was observed. Women showed a significant increase in sex hormone-binding globulin (SHBG) levels, while total testosterone (TT) levels and the free androgen index decreased significantly. Furthermore a significant decrease in hirsutism was observed. There was a decrease in cholesterol and an increase in high-density lipoprotein., Conclusions: Long-term treatment with metformin in women with PCOS appears to reduce androgen excess due to increased SHBG and decreased TT levels resulting in improvement of hirsutism as a clinical sign of androgen excess. Furthermore a significant decrease in fasting and 2-h insulin levels and slightly improved insulin resistance indices were observed., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: The most common treatment regimen in female-to-male transsexuals is administration of short-acting testosterone esters intramuscularly every 2 weeks., Aim: The aim of this study was to evaluate the effect of long-acting intramuscular testosterone undecanoate on body composition and bone mineral density during cross-sex hormone therapy in female-to-male transsexuals., Methods: Forty-five female-to-male transsexuals (FtMs) were treated with injections of testosterone undecanoate 1,000 mg intramuscularly every 12 weeks over 24 months., Main Outcome Measures: Body composition, bone mineral density, hormone parameters, and lipids were compared after 12 months and after 24 months with baseline values. Sonographic findings in the ovaries and endometrium, clinical and adverse effects during the study period were recorded., Results: There was a significant increase in lean mass in the FtMs during the study period in comparison with baseline values, whereas no change in BMI, fat mass, and bone mineral density was observed. There was a significant decline in gonadotropins, estradiol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, and high-density lipoprotein, while testosterone and triglyceride levels increased significantly after 12 and 24 months. Ovaries remained unchanged and no noticeable endometrial pathology was observed. No mortality or morbidity was observed during the study period. We observed a cessation of menstrual bleeding, an increase in clitoral growth, libido, body and beard hair growth, deepened voices and decline in breast size. There was a significant increase in hemoglobin, hematocrit, glutamic-pyruvic transaminase, gamma-glutamyl transferase, and an increase in systolic blood pressure during the study period., Conclusions: There was an increase in lean mass during the study period in FtMs treated with testosterone undecanoate. Transsexual patients should be monitored for adverse effects on lipid profiles, blood pressure, and erythrocytosis during intramuscular testosterone undecanoate therapy., (© 2010 International Society for Sexual Medicine.)

Background: Uterus transplantation is the only way for women with no functional uterus to become pregnant. However, the technique is limited by the fact that an aggressive immunosuppression is necessary in order to avoid rejection of the graft. For better chances of finding a matching organ, which would minimize the immunosuppressive therapy, the establishment of cryobanks with a large number of uteri would be helpful. The aim of this study was to evaluate the feasibility to cryopreserve sheep uteri and to review the literature in this exciting new field of uterus cryopreservation and transplantation., Material and Methods: Ten sheep uteri were frozen either with slow cooling after perfusion with 10% dimethylsulfoxide, or without perfusion and the contractile ability was compared with that of fresh uteri., Results: All perfused uteri showed contractions after thawing, similar to those of the non-frozen uteri., Conclusion: This study shows that the perfusion of sheep uterus with a cryoprotectant prior to slow freezing allows the cryopreservation of the whole organ and maintains the functionality of the organ after thawing. The perfused sheep uterus provides an experimental model for further investigations with other cryoprotective agents and freezing protocols.

Objective: To evaluate the impact of smoking on endocrine, metabolic, and clinical parameters in women with polycystic ovary syndrome (PCOS)., Design: Cohort analysis., Setting: University hospital., Patient(s): 346 women with PCOS, including 98 smokers and 248 nonsmokers., Intervention(s): Screening panel, including physical examination, weight and height measurement, and ultrasound examination of the ovaries, and hormone and insulin measurements., Main Outcome Measure(s): Clinical, metabolic, and endocrine parameters, oral glucose tolerance test, calculation of insulin resistance indexes., Result(s): In women with PCOS, smoking was associated with statistically significantly increased levels of fasting insulin and calculated free testosterone (cFT) and with a raised free androgen index (FAI) score, which resulted in aggravated scores on the homeostatic model for assessment of insulin resistance (HOMA-IR). However, no differences were observed between the smoking and nonsmoking groups with regard to the clinical parameters for hirsutism, acne, ovulatory function (classified as eumenorrhea, oligomenorrhea, and amenorrhea), or polycystic ovaries using the ultrasound criteria recommended according to the Rotterdam definition., Conclusion(s): In women with PCOS, smoking is associated with increased free testosterone and fasting insulin levels, resulting in aggravated insulin resistance. However, there were no differences between smokers and nonsmokers when clinical parameters were compared., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The objective of the study was to examine the uterine contractions and the arterial perfusion pressure changes after application of oxytocin, endothelin 1, prostaglandins PGE(1), PGE(2) and PGF(2alpha), in order to identify the substance with the greatest intrauterine pressure (IUP)/intra-arterial pressure (IAP) ratio, which means the substance most suitable for inducing uterine contractility without raising the systemic vascular pressure. Increasing doses of oxytocin, endothelin 1, PGE(1), PGE(2) and PGF(2alpha) were applied as bolus injection through the uterine artery of perfused swine uteri and the intrauterine and intra-arterial pressure rises were recorded. All substances showed a significant cervicofundic pressure gradient and, with the exception of PGF(2alpha), the uterine peristalsis moved towards the cervix uteri. The perfusion pressure after application of oxytocin, PGE(1), PGE(2) and PGF(2alpha) reached a maximum value and started to decrease, whereas endothelin 1 caused a continuous increase in the perfusion pressure. Endothelin 1 showed the lowest IUP/IAP ratio and oxytocin the greatest. In conclusion, the IUP/IAP ratio provides a promising new parameter for the study of uterine contractility physiology. Besides oxytocin, PGE(2) and PGF(2alpha) emerged as the best candidate substances to improve uterine contractility without raising the intra-arterial pressure., (Copyright 2009 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Today the vast majority of children and adolescents diagnosed with cancer achieve relatively high rates of remission and long-term survival, due to significant advances in oncological treatment. Oncological surgery, radiotherapy and chemotherapy however, are often detrimental to fertility, thus substantially impacting a patient's quality of life. Concerns about fertility are similar for men and women; however, their opportunities for intervention differ considerably. This article reviews the literature, discusses the etiology and effects of cancer treatment on fertility, and presents the current and emerging options for the preservation of fertility in patients with cancer. The various diagnostic methods of assessing the fertility potential at the time of diagnosis and the efficacy of the different fertility preserving methods after cancer treatment are also presented.

Objective: To investigate the contractile response of the perfused swine uterus to various receptor pathways (oxytocin, prostaglandins, and muscarine)., Design: An extracorporeal perfusion model of the swine uterus was used that keeps the uterus in a functional condition and is appropriate for the study of physiologic questions., Intervention(s): Oxytocin-, prostaglandin-, and carbachol-induced uterine contractility and peristalsis were assessed using an intrauterine double-chip microcatheter., Setting: University hospital., Main Outcome Measure(s): Intrauterine pressure profiles., Result(s): A dose-dependent increase in intrauterine pressure (IUP) in the isthmus uteri and corpus uteri was observed after the administration of prostaglandin F(2alpha) (PGF(2alpha)) and oxytocin, which reached a plateau after further stimulation. A dose-dependent increase in IUP in the isthmus uteri and corpus uteri was also observed after the administration of prostaglandin E(1) (PGE(1)) and prostaglandin E(2) (PGE(2)), with a plateau in IUP in the middle-concentration range and a decrease during the further course of stimulation. After administration of PGE(1), PGE(2), and PGF(2alpha), different directions of contraction waves were also observed. Carbachol also showed a unique contractility pattern, with isolated, very powerful, dose-dependent contractions with an IUP gradient, suggesting directed transport from the upper region to the lower region., Conclusion(s): This study demonstrated that oxytocin, the prostaglandins, and carbachol modulate contractility in nonpregnant swine uteri in a characteristic way, resulting in different contractility patterns.

Objective: It has been reported that hypoactive sexual desire disorder (HSDD) affects one-third of transsexual women (defined as postoperative male-to-female transsexuals) receiving estrogen replacement whose bioavailable androgen levels are lower than in ovulating women and comparable with those in surgically postmenopausal women. The aim of this study was to evaluate the efficacy of transdermal testosterone treatment and of oral dydrogesterone in transsexual women with HSDD receiving estrogens., Methods: Seven transsexual women with HSDD were treated with a testosterone patch and nine transsexual women with HSDD were treated with oral dydrogesterone over 24 weeks. The primary end point was the change in the brief profile of female sexual function (B-PFSF) score. Secondary end points were changes in hormonal parameters and side effect assessments., Results: A significant increase in total testosterone and free testosterone levels was observed in the group receiving transdermal testosterone. At 24 weeks, there was a significant improvement in the B-PFSF score showing an improvement in sexual desire among transsexual women treated with the testosterone patch, whereas no change in the B-PFSF score was observed in transsexual women treated with oral dydrogesterone. No side effects were reported., Conclusions: In this pilot study, sexual desire in transsexual women improved significantly after treatment with the testosterone patch, without noticeable side effects.