Comparison of dienogest and progesterone effects on uterine contractility in the extracorporeal perfusion model of swine uteri.

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.

Fertility Preservation for Patients with Malignant Disease. Guideline of the DGGG, DGU and DGRM (S2k-Level, AWMF Registry No. 015/082, November 2017) - Recommendations and Statements for Girls and Women.

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.

Operative techniques and complications of extraction and transplantation of ovarian tissue: the Erlangen experience.

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.

Effects of interactions between progesterone and prostaglandin on uterine contractility in a perfused swine uterus model.

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.

Offspring after embryo-preserving biopsy of the embryoblast with standard ICSI equipment in mouse blastocysts.

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.

Thyroid hormone receptors and reproduction.

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.

Effects of intramuscular testosterone undecanoate on body composition and bone mineral density in female-to-male transsexuals.

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.

The impact of testosterone administration to female-to-male transsexuals on insulin resistance and lipid parameters compared with women with polycystic ovary syndrome.

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.

Smoking is associated with increased free testosterone and fasting insulin levels in women with polycystic ovary syndrome, resulting in aggravated insulin resistance.

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.

Effects of transdermal testosterone or oral dydrogesterone on hypoactive sexual desire disorder in transsexual women: results of a pilot study.

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.

Hormonal and histologic findings in human cryopreserved ovarian autografts.

This is the first report showing a hormonal and histologic discrepancy in cryopreserved human ovarian tissue 11 months after orthotopic autotransplantation. The presence of antral follicles was observed although the hormonal values had returned to castrated levels.

First retransplantation of cryopreserved ovarian tissue following cancer therapy in Germany.

INTRODUCTION: New anticancer treatments have increased survival rates for cancer patients but often at the cost of sterility. One way of preserving fertility in these patients is the use of cryopreservation of ovarian tissue with subsequent retransplantation following a period of recurrence-free survival. We report the follow-up of the first case of retransplantation of ovarian tissue in Germany. METHODS: Immediately following the diagnosis of anal cancer, ovarian tissue was removed laparoscopically, and cryopreserved. The patient was then treated with combined radiochemotherapy, which resulted in iatrogenic premature ovarian failure, and was associated with inhibin B serum levels lower than 10 ng/L. After the 2.5 year period of cancer remission, the cryopreserved ovarian tissue was retransplanted orthotopically. RESULTS: Five months later estradiol serum levels had risen from lower than 20 pg/mL to 436 pg/mL. Three ovarian follicles were detected ultrasonographically in the pelvic side wall. Finally the patient reported her first menstruation after the intervention. The endocrine activity of the transplanted cryopreserved tissue has demonstrated viability, and the ability to develop. DISCUSSION: Cycle monitoring and timed intercourse should now help to achieve conception. These first results from Germany for retransplantation of cryopreserved ovarian tissue clearly show its potential for preserving fertility.

Low sex hormone-binding globulin as a predictive marker for insulin resistance in women with hyperandrogenic syndrome.

BACKGROUND: The aim of the present study is to assess insulin resistance (IR) in women with hyperandrogenic syndrome, which was suggested to replace the term polycystic ovary syndrome by the Androgen Excess Society, and to evaluate whether sex hormone-binding globulin (SHBG) can be used as a predictive marker of IR in hyperandrogenic women. METHODS: Clinical, metabolic, and endocrine parameters were measured, and an oral glucose tolerance test was carried out. The women were classified as IR group or non-IR group, in accordance with defined cutoff points for the homeostatic model assessment of IR (HOMA-IR) at > or =2.5, the quantitative insulin sensitivity check index at < or = 0.33, and the Matsuda insulin sensitivity index (ISI) at < or = 5. RESULTS: The women classified as having IR had a significantly higher body mass index (BMI) and free androgen index (FAI) and showed significantly lower SHBG and high-density lipoprotein (HDL) levels, regardless of the indices used. However, with the Matsuda ISI, generally more women were diagnosed as having IR, and this group had significantly higher total testosterone and triglyceride values, as well as a higher incidence of hirsutism. CONCLUSIONS: Women who were classified as being insulin resistant using insulin sensitivity indices showed significantly higher BMI and FAI values and lower SHBG and HDL levels. However, the Matsuda ISI may be more favorable for identifying IR in hyperandrogenic women. SHBG may serve as a predictive marker of IR in these women, particularly in those who are obese.

The VCUAM (Vagina Cervix Uterus Adnex-associated Malformation) classification: a new classification for genital malformations.

OBJECTIVE: With an incidence of up to 5% in the general population, genital malformations are a frequent clinical occurrence. However, using the existing published classifications of malformations, difficulties arise in classifying genital malformations appropriately. The aim of the present study was to produce a simple, systematic, and reproducible classification system. DESIGN: A systematic arrangement of genital and associated malformaltions, using a structure similar to that in the TNM classification of oncological tumors, was developed and validated. SETTING: Patients with genital malformations in a university hospital. PATIENT(S): Ninty-nine premenopausal patients with genital malformations. INTERVENTION(S): Patients were diagnosed for genital malformation using laparoscopy or magnetic resonance imaging. MAIN OUTCOME MEASURE(S): A new classification (VCUAM) is presented to evaluate patients with different genital malformations. RESULT(S): The external and internal female genital organs were divided into the following subgroups in accordance with the anatomy: vagina (V), cervix (C), uterus (U), and adnexa (A). Associated malformations were assigned to a subgroup (M) relative to each specific organ. The classification was validated in a group of 99 patients with genital malformations. CONCLUSION(S): The VCUAM classification for the first time makes it possible to reflect even complex malformations in a precise and individual fashion, taking associated malformations into account. The classification makes it easier to provide appropriate clinical care for the affected patients.