Impact of vaginal estriol on serum hormone levels: a systematic review.

The genitourinary syndrome of menopause (GSM) affects up to 84% of postmenopausal women and may significantly reduce the quality of life in some. For symptom relief, there are several non-hormonal and hormonal vaginal products available. In Europe, vaginal estriol (E3) is the most frequently chosen estrogen for GSM treatment. The aim of this systematic review was to assess the impact of vaginal E3 on serum sex hormone levels, an outcome that has been previously used to assess safety in similar products. In our review, we did not find any alterations in serum estrone, estradiol, testosterone, progesterone and sex hormone binding globulin levels after vaginal E3 application. In contrast, some studies showed a minimal and transient decrease in serum gonadotropin levels, which however remained within the postmenopausal range. Similarly, only a few studies reported a minimal and transient increase of serum E3 levels, with the rest reporting no changes. The lack of clinically relevant long-term changes in serum sex hormone levels supports the current literature providing evidence about the safety of vaginal E3 products.

Ultra-low dose - new approaches in menopausal hormone therapy.

Despite increasing life expectancy, the age of onset of natural menopause has not significantly changed in recent decades. Thus, women spend about one-third of their lives in an estrogen-deficient state if untreated. There is a need for appropriate treatment of acute symptoms and prevention of the sequelae of chronic estrogen deficiency. International guidelines call for the use of the lowest effective hormone dosage for vasomotor symptom relief, the major indication for menopausal hormone therapy (MHT). In 2011, an oral continuous combined ultra-low-dose MHT was approved in Switzerland. This publication was elaborated by eight national menopause specialists and intends to review the advantages and disadvantages of ultra-low-dose MHT after the first years of its general use in Switzerland. It concludes that, for many women, ultra-low-dose MHT may be sufficient to decrease vasomotor symptoms, but not necessarily to guarantee fracture prevention.

[Fertility preservation techniques in women of reproductive age ]. / Techniques de préservation de la fertilité chez la femme en âge de procréer.

As a result of advances in oncologic treatment, a growing number of women diagnosed with cancer may envisage cure. Young women diagnosed with cancer often have a desire to fall pregnant in the future or may even be diagnosed with cancer in the process of family planning. The potential gonadotoxic effect of certain chemotherapeutic agents is well described. Therefore, it is essential that all women concerned about their fertility receive counselling from a reproductive medicine specialist to discuss the fertility preservation options. Currently, ovarian stimulation with cryopreservation of oocytes or fertilized oocytes is the treatment of choice. However, other options such as in vitro maturation or ovarian tissue cryopreservation should be discussed if ovarian stimulation is contraindicated.

[New child wish after vasectomy: vasovasostomy or assisted reproductive medicine?]. / Désir de grossesse après vasectomie: vasovasostomie ou procréation médicalement assistée?

New child wish after vasectomy: vasovasostomy or assisted reproductive medicine? In the case of a new child wish after vasectomy, there are two options: vaso-vasostomy (VV) or biopsy of the testicle associated with intra-cytoplasmatic sperm injection (ICSI). Both methods are not reimbursed. The VV offers a cumulative pregnancy rate of 28-40%, depending on pre-, intra- and postoperative factors. The age of the female partner and the time after vasectomy are the most important factors. Pregnancy rates after ICSI are 29-41% per transfer. Cumulative pregnancy rates vary between 60-80%. Malformation rates after ICSI in this special collective are not investigated yet, the "general" ICSI-collective differs completely compared to the a priori fertile couples after vasectomy. Couples have to inform themselves about the experience of the doctors and their rate of success in order to minimize the risk of failure.

[The impact of obesity on fertility]. / Obésité et fertilité ne font pas bon ménage.

There are many negative impacts of obesity on fertility. Obese couples present decreased sperm count, decreased ovulation and conception rates, increased erectile dysfunction and spontaneous abortion rate as well as increased maternal and foetal complications of pregnancy. Moreover, obesity tends to decrease response to fertility treatments. Fortunately, intensive lifestyle modifications can restore fertility while decreasing pregnancy complications risk. With the increasing trend of obesity to affect young populations, taking care of these infertile couples rapidly is capital to restore fertility and decrease its related pregnancy complications.

Serum hyperglycosylated human chorionic gonadotropin to predict the gestational outcome in in vitro fertilization/intracytoplasmic sperm injection pregnancies.

Hyperglycosylated human chorionic gonadotropin (H-hCG) is secreted by the placenta in early pregnancy. Decreased H-hCG levels have been associated with abortion in spontaneous pregnancy. We retrospectively measured H-hCG and dimeric hCG in the sera of 87 in vitro fertilization patients obtained in the 3 weeks following embryo transfer and set the results in relation to pregnancy outcome. H-hCG and dimeric hCG were correlated (r(2) = 0.89), and were significantly decreased in biochemical pregnancy (2 microg/l and 18 IU/l, respectively) compared to early pregnancy loss (22 microg/l and 331 IU/l) and ongoing pregnancy (32 microg/l and 353 IU/l). Only H-hCG tended to discriminate between these last two groups.

Androgen and gonadotropin patterns differ in HIV-1-infected men who develop lipoatrophy during antiretroviral therapy: a case-control study.

OBJECTIVES: We compared androgen and gonadotropin values in HIV-infected men who did and did not develop lipoatrophy on combination antiretroviral therapy (cART). METHODS: From a population of 136 treatment-naïve male Caucasians under successful zidovudine/lamivudine-based cART, the 10 patients developing lipoatrophy (cases) were compared with 87 randomly chosen controls. Plasma levels of free testosterone (fT), dehydroepiandrosterone (DHEA), follicle-stimulating hormone and luteinizing hormone (LH) were measured at baseline and after 2 years of cART. RESULTS: At baseline, 60% of the cases and 71% of the controls showed abnormally low fT values. LH levels were normal or low in 67 and 94% of the patients, respectively, indicating a disturbance of the hypothalamic-pituitary-gonadal axis. fT levels did not significantly change after 2 years of cART. Cases showed a significant increase in LH levels, while controls showed a significant increase in DHEA levels. In a multivariate logistic regression model, lipoatrophy was associated with higher baseline DHEA levels (P=0.04), an increase in LH levels during cART (P=0.001), a lower body mass index and greater age. CONCLUSIONS: Hypogonadism is present in the majority of HIV-infected patients. The development of cART-related lipoatrophy is associated with an increase in LH and a lack of increase in DHEA levels.

Surplus embryos in Switzerland in 2003: legislation and availability of human embryos for research.

Legislation influences the availability of embryos for research. The law in Switzerland, and in some other European countries, is restrictive concerning medically assisted reproduction and stem cell research. Swiss law prohibits the creation of embryos for research purposes. It permits the derivation of human embryonic stem cells for research from surplus embryos but prohibits research with intact surplus embryos and embryo donation to other couples. Swiss law defines all embryos generated during a reproductive cycle and not used for reproduction as surplus embryos. The aim of this study was to evaluate the surplus embryos generated in Switzerland in 2003. A detailed questionnaire was sent to all registered IVF units in Switzerland (n = 22). 11727 embryos were generated during 2003. Of these, 93.5% were transferred into the uterus and 0.4% were cryopreserved. The remaining 6.1% (n = 711) became surplus. Of these, 2.7% were transferred intravaginally and the rest discarded due to poor quality (1.6%), development arrest (1.5%), renunciation by the couple (0.2%) or for other reasons (0.1%). The number of surplus embryos in Switzerland in 2003 was evaluated. Most surplus embryos became so during a therapeutic cycle. The restrictive legal regulation decreases the availability of human embryos for research.

Serum leptin and C-reactive protein levels in the physiological spontaneous menstrual cycle in reproductive age women.

OBJECTIVE: Only a few studies have investigated variations of different markers for inflammatory processes during the physiological menstrual cycle. The results are conflicting, particularly concerning the correlation between the marker leptin and steroid hormones. The aim of the study was to investigate the inflammatory markers C-reactive protein (CRP) and leptin in the serum of healthy, normally ovulating women and to correlate these with each other and with the hormones of the gonadal axis. A cycle-dependence of the markers studied would imply an exact timing of the blood sampling for clinical needs. DESIGN: Observational study investigating the two inflammatory markers CRP and leptin in relation to the hormonal pattern of the gonadal axis during the normal cycle. METHODS: Ovulatory cycles of 36 healthy, young, normo-androgenic women, having a normal body mass index were evaluated. Serum concentrations of leptin and CRP, as well as of follicle-stimulating hormone, luteinising hormone, 17beta-oestradiol, progesterone, prolactin (PRL) and free testosterone were measured every 1-2 days during one full cycle. RESULTS: Serum levels of leptin and CRP behaved differently during ovulatory cycles, with higher concentrations for leptin only during certain phases. Significant correlations were found in the follicular phase between leptin and PRL and leptin and free testosterone. CONCLUSIONS: Leptin levels change during the menstrual cycle. Leptin levels are more stable on cycle days 1-5 than later in the cycle. For precise cycle-independent measurements, these fluctuations have to be taken into account. There is no similar cyclic pattern for CRP.

Lack of seasonal variations in fertilization, pregnancy and implantation rates in women undergoing IVF.

BACKGROUND: Several studies have investigated seasonal variations during IVF. Their results are contradictory, especially concerning fertilization and pregnancy rates. The aim of the present study was to re-evaluate these parameters using a large number of IVF cycles. METHODS: A total of 7368 IVF cycles conducted in Switzerland between 1995 and 2003 were retrospectively analysed. To avoid a bias in the evaluation of the fertilization rate, only IVF cycles without ICSI were considered for analysis. Cycles were assigned to seasons according to the date of the beginning of stimulation. RESULTS: There were no statistically significant differences between the seasons concerning the fertilization, the pregnancy and the implantation rates. However, statistically significant variables deciding on the outcome of an IVF cycle are age, centre, aetiology of infertility and day of transfer. CONCLUSIONS: There were no statistically significant seasonal differences in central Europe (Switzerland) that influenced the outcome of IVF treatment. The only statistically significant variables of IVF outcome were age, centre, aetiology of infertility and day of transfer. A change to routine fertility treatment concerning the different seasons should therefore not be taken into account.

Concentrations of leptin and C-reactive protein in serum and follicular fluid during assisted reproductive cycles.

BACKGROUND: There are only a few studies that have investigated inflammatory processes during ovarian hyperstimulation, with contradictory results especially concerning outcome. The aim of the study was to investigate the inflammatory markers C-reactive protein and leptin in serum and follicular fluid and to correlate these with the outcome. METHODS: One hundred and sixty-two gonadotrophin stimulated cycles were evaluated. Serum concentrations of leptin and C-reactive protein were measured at the initiation of stimulation, on the day of hCG administration or the day before, and on the day of oocyte retrieval. They were also determined in the follicular fluid. RESULTS: Serum leptin and C-reactive protein levels increased significantly during stimulation until the day of oocyte pick up, but following different patterns. After stimulation, they correlated with each other in serum and follicular fluid, but not with estradiol or progesterone concentration, embryo quality, or the pregnancy rate. CONCLUSIONS: Leptin and C-reactive protein levels change significantly during assisted reproductive treatment. In contrast to estradiol they are, however, not a marker of success.

[Antiretroviral therapy and pregnancy]. / Antiretrovirale Medikamente und Schwangerschaft.

Whereas the perinatal transmission rate with untreated HIV positive women is around 30%, the results of Pediatric AIDS Clinical Trials Group in 1994 showed a reduction by nearly 70% with Zidovudin chemoprophylaxis. The transmission rate can even be reduced to under 2%, if a cesarean section before onset of labour and before premature rupture of membranes is done in addition. An individualized, optimal antiretroviral combination therapy, ideally introduced in the second trimenon (in special cases even already in the first trimenon), is of great importance. As a further strategy of prevention of perinatal transmission, intravenous Zidovudin chemoprophylaxis should be given in addition to the mother during labour and to the newborn during the first six weeks of life. Besides very few exceptions, long-term data after intrauterine administration of antiretroviral therapy do not show any teratogen or other long term consequences to date. The situation in developing countries is very critical with still high transmission rates because of the lack of antiretroviral therapy due to logistical reasons and costs and the need of breastfeeding. For these reasons, more and more feasible short protocols are developed with at least fifty percent reduction of neonatal transmission rates.

Maternal serum levels of placental proteins after in vitro fertilisation and their implications for prenatal screening.

OBJECTIVES: To determine whether the serum levels of pregnancy-associated plasma protein A (PAPP-A), pregnancy-specific beta(1)-glycoprotein (SP1), placental lactogen (hPL) and human chorionic gonadotrophin (hCG) are different in pregnancies obtained after in vitro fertilisation (IVF) and embryo transfer (ET) in comparison to spontaneous pregnancies. Assessment of the need to establish normal medians for biochemical trisomy screening in IVF pregnancies. METHODS: The population comprised 96 IVF-ET pregnancies, of which 79 came from fresh gonadotrophin-stimulated cycles and 17 from embryo transfers without gonadotrophin stimulation (natural cycle IVF, frozen embryo transfers), and 156 spontaneous pregnancies. A single blood sample was obtained between 7 + 0 and 16 + 3 weeks. PAPP-A, SP1, hPL and hCG were quantified and the levels compared between gonadotrophin-stimulated IVF, steroid-only- or non-stimulated IVF, and controls with respect to gestational age using non-parametric statistical analysis. RESULTS: PAPP-A and hPL levels were reduced after stimulated IVF in early gestation (before 10 pregnancy weeks); SP1 followed the same trend without reaching statistical significance. hCG tended to be increased after IVF treatment including non-gonadotrophin-stimulation cycles, and also beyond 10 pregnancy weeks. CONCLUSION: Reduced PAPP-A with increased hCG yields an increased risk in screening for foetal trisomy 21. We confirm recently published observations but do not recommend the establishment of normal medians for IVF pregnancies since the extent of the deviations is varying according to the different stimulation protocols and dosages of gonadotrophins used.

[Diabetes mellitus and pregnancy: screening and therapy]. / Diabetes mellitus und Schwangerschaft: Screening und Therapie.

There are two entities to differentiate: 1. Diabetes in pregnancy (pre-existent type 1 or type 2 diabetes with tendency of deterioration during pregnancy or first occurrence of a type 1 or type 2 diabetes with persistence after pregnancy. 2. Impaired Glucose Tolerance = IGT (Diagnosis of an impairment of glucose tolerance during pregnancy) Aims of the screening are the avoidance of complications for mother and child. There is no uniform consent regarding screening during pregnancy. With pregnant women without risk factors, the blood sugar is determined without eating and drinking in plasma between 24 and 28 weeks of gestation. If values are > 4.8 mmol/l, an oral 75 g glucose tolerance test is carried out. Alternatively, a 50 g oral glucose tolerance test can be made. With pregnant women with risk factors, we already carry out an oral 75 g glucose tolerance test in the first trimester. If the values are normal, we repeat the 75 g glucose tolerance test between 24 and 28 weeks of gestation. Main pillars of therapy are diet and movement. In gestational diabetes, an insulin therapy is indicated if blood sugars are too high, fetal growth is sonographically accelerated or a polyhydramnion is present. Oral antidiabetic medicaments are contraindicated during pregnancy. Pregnancies with diabetes in pregnancy or gestational diabetes are risk pregnancies, which are controlled more intensively. Delivery is ideally at term or with confirmed lung maturity. If an impaired glucose tolerance is diagnosed during pregnancy, an oral 75 g glucose tolerance test as well as annually blood sugar controls are carried out because of the augmented risk of developing a type 2 diabetes later in life.

Lactoperoxidase inhibits glucosyltransferases from Streptococcus mutans in vitro.

This study examines the possible effect of the antimicrobial peroxidase system on the activity of streptococcal glucosyltransferases B, C and D (GtfB, GtfC and GtfD), either in solution (GtfB and GtfC) or when adsorbed to hydroxyapatite (GtfC and GtfD) at pH 6.5. The lactoperoxidase (LP) system (LP, H(2)O(2), SCN(-)) had no effect on the activity of dissolved GtfC, but the activity of dissolved GtfB was enhanced. The LP system, however, strongly inhibited the activities of both GtfC and GtfD in their adsorbed form. LP enzyme, without its substrates, inhibited all three Gtf enzymes: GtfB and GtfC in concentrations between 10 and 100 microg/ml in liquid phase and adsorbed GtfC and GtfD in concentrations between 25 and 50 microg/ml. This inhibition was in part abolished in liquid phase, but not in solid phase, if the substrates of LP were added. This study shows that the lactoperoxidase system can exert inhibitory activity against streptococcal Gtfs without generating oxidizing agents.

[Hormonal contraception for adolescents]. / Hormonale Kontrazeption bei Adoleszenten.

The new hormonal contraceptives are safe, effective and with fewer side effects than the older formulations. Their incidence of serious complications is low, particularly as compared to the health risk related to pregnancy. Adolescents must be screened for contra-indications before giving them a hormonal contraceptive. Because pills do not prevent sexually transmitted diseases, teenagers should be counselled to use a barrier methods together with COCs. Young girls need frequent follow-up and close monitoring to minimise side effects and to increase compliance and continuation in use. Long-term contraception by implants represents a valid alternative option with an increasing popularity among adolescents.

[Hormonal contraception in the perimenopause]. / Hormonale Kontrazeption in der Perimenopause.

Perimenopause, such as postmenopause, is a physiologic condition that could be accompanied by several symptoms that may need a medical intervention. Women need to be informed about the available therapeutic options, including no treatment at all if not necessary. Oral hormonal contraceptives represent a valid and safe option in healthy premenopausal women with complaints. They guarantee a safe and reliable contraception in women without contraindications. The alternatives to oral hormonal contraceptives are injectable progestagens, oral progestagen-only preparations, progestagen implants or progestagen-loaded IUD's. It is highly important to inform correctly the patient and make her to participate actively in the therapeutic decision. This educational process helps in building a solid relationship and improves patient adherence with better clinical results.

Properties of Streptococcus sanguinis glucans formed under various conditions.

The aim of our study was to determine whether the structure of glucans formed by glucosyltransferase from Streptococcus sanguinis (GtfSs) on a surface differ from those formed in solution and to explore the effects of antiserum to Gtfs, control normal rabbit serum, starch hydrolysates (STH) and dextran on S. sanguinis (GtfSs) glucan. Linkage analyses showed that solution-formed glucans are predominantly alpha-1,6-linked and have a small amount of alpha-1,3-linked glucose. Surface-formed glucans have enhanced susceptibility to mutanase. Solution- and surface-formed glucans made in the presence or absence of sera, STH, and dextran contain linkages which differ in both amount and type from control glucans. The GtfSs enzyme in solution exposed to antiserum behaves as if it is adsorbed to a surface. Binding of Streptococcus mutans GS-5 and Actinomyces viscosus OMZ105E (Ny1) to S. sanguinis glucan differs if the glucan is formed in the presence of antiserum. The information could help to define the role of glucans in the formation of pellicle, colonization of tooth surfaces and the accumulation of dental plaque.

Effects of antibodies to glucosyltransferase on soluble and insolubilized enzymes.

OBJECTIVE: Previous studies have shown that glucosyltransferase enzymes (Gtfs) of Streptococcus mutans adsorbed to saliva coated hydroxyapatite (sHA) have distinct properties from the same enzymes in solution. The purpose of the present study was to determine the effects on enzyme activity of polyclonal antibodies raised to Gtfs in a soluble form and bound to sHA. MATERIALS AND METHODS: Antiserum was raised in six New Zealand White rabbits using the purified glucosyltransferase enzymes (Gtfs) of S. mutans, GtfB, GtfC, or GtfD as soluble antigens or adsorbed to hydroxyapatite (HA, insolubilized). The antisera were examined for their ability to react to these Gtfs and Gtf from Streptococcus sanguis (GtfSs) in Western blot formats as well as inhibit enzyme activity in solution and insolubilized. RESULTS: Antibodies raised against GtfB or GtfC detected all Gtf enzymes examined in Western blots; antibodies raised to GtfD reacted strongly to GtfD and GtfSs, poorly to GtfC, and was non-reactive with GtfB. Antibodies to GtfB or GtfC inhibited activity of GtfB and GtfC in solution by 90% or more. Enzyme activity adsorbed to sHA was inhibited from 70% to 80% by the same antisera. These same antibodies possessed no specific effect on the activities of either GtfD or GtfSs. Antibodies raised to the GtfD enzyme inhibited activity of GtfD (80% to 90% inhibition) and GtfSs activity (50% to 80%) in solution. In contrast the GtfD antibodies had no effect on the activity of either GtfB or GtfC enzymes in solution. Modest inhibitory effects were noted on GtfC and GtfSs enzymes bound to sHA, but no inhibition was observed for sHA-bound GtfB or GtfD. CONCLUSION: These data show that some antibodies effective against enzymes in solution may have significantly lesser inhibitory effects against the same enzymes insolubilized. Further, presentation of Gtf antigen immobilized to HA has only a minor influence on the production of antibodies inhibitory to Gtf activity.

Studies concerning the glucosyltransferase of Streptococcus sanguis.

We have shown in previous studies that the glucosyltransferase (Gtf) enzymes of Streptococcus mutans have distinct properties when adsorbed to a surface. In the present study, we compared the activity of Gtf from Streptococcus sanguis, designated GtfSs, in solution and on the surface of saliva-coated hydroxyapatite (sHA) beads, and determined the ability of its product glucan to support the adherence of oral microorganisms. Gtf from S. sanguis 804 NCTC 10904 was purified from culture supernatant fluids by means of hydroxyapatite chromatography. Enzyme and the substrate were prepared in buffers at pH values from 3.5 to 7.5. Maximum activity of GtfSs occurred between pH 5.5 and pH 6.5, whether in solution or adsorbed onto a surface. The solubilized and insolubilized enzymes showed highest activity at 40 degrees C; activity was reduced by 50(+/-2)% at 20 and 30 degrees C. The enzyme did not form glucans in either phase at 10 or 60 degrees C. The K(m), determined from Lineweaver-Burk plots, for the enzyme in solution was 4.3(+/-0.4) mmol/l sucrose, and the K(m) for the enzyme on sHA beads was 5.0(+/-1.0) mmol/l sucrose. The ability of the GtfSs glucan synthesized on the surface of sHA beads to support the adherence of oral bacteria was investigated. (3)H-thymidine-labeled bacteria (S. mutans GS-5, S. sobrinus 6715, S. sobrinus 6716, S. sanguis 10904, Actinomyces viscosus OMZ105E, A. viscosus 2085, and A. viscosus 2086) were incubated with sHA beads coated with GtfSs glucan. S. mutans GS-5 displayed the highest level of binding numerically. These results show that the GtfSs of S. sanguis is active on sHA beads, that the pH optimum for activity on a surface differs slightly from that in solution, and that its product glucan can support the adherence of oral microorganisms.