Torsten Frambach

Ovarian stimulation to cryopreserve fertilized oocytes in cancer patients can be started in the luteal phase.

OBJECTIVE To analyze if oocytes can be obtained in all patients before cancer treatment within 2 weeks by initiating ovarian stimulation during the follicular or luteal phase. DESIGN Prospective controlled multicenter trial. SETTING Four university-based centers. PATIENT(S) Forty cancer patients before chemotherapy. INTERVENTION(S) Twenty-eight patients were stimulated with gonadotropins in the follicular phase (group I). In 12 patients (group II), ovarian stimulation was initiated in the luteal phase, and these received GnRH antagonists and recombinant FSH. In 14 patients, 143 oocytes were further processed for fertilization by intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S) Number of oocytes aspirated after ovarian stimulation, cumulative FSH/hMG dosage, viability and maturity of oocytes, and fertilization rate by ICSI. RESULT(S) Patients in group I (age 27.6 +/- 4.9 yrs) were stimulated on average for 10.6 days, and patients in group II (age 31.2 +/- 5.7 yrs) for 11.4 days. Total amount of FSH was on average 2,255 IU (I) and 2,720 IU (II) per patient. Average and median numbers of aspirated oocytes were, respectively, 13.1 and 11.5 (I) versus 10.0 and 8.5 (II); 83.7% (I) and 80.4% (II) of the oocytes were mature and viable and could be treated by ICSI. Fertilization rate was 61.0% (I) versus 75.6% (II). CONCLUSION(S) This pilot study suggests that oocytes can be obtained before cancer treatment efficiently irrespective of the phase of the menstrual cycle.

Expression of transketolase‐like 1 (TKTL1) and p‐Akt correlates with the progression of cervical neoplasia

Aim:  It is supposed that increased glycolysis is crucial for the energy supply during tumor progression. Unfortunately, the relevance of glycolysis in cervical neoplasia is unknown, but what is certain is the fact that cervical cancer shows a high expression of glucose membrane transporters, which are necessary for glucose uptake as an energy source. Transketolase‐like enzyme 1 (TKTL1) and the oncogene p‐Akt have been described to play an important role in glycolysis during tumorigenesis. Thus, we were interested in their expression in cervical tissue.

Microbial Quorum-Sensing Molecules Induce Acrosome Loss and Cell Death in Human Spermatozoa

ABSTRACT Infertility in men and women is frequently associated with genital contamination by various commensal or uropathogenic microbes. Since many microorganisms are known to release quorum-sensing signals in substantial amounts, we raised the question whether such molecules can directly affect human spermatozoa. Here we show that farnesol and 3-oxododecanoyl-l-homoserine lactone, employed by the opportunistic pathogenic yeast Candida albicans and the gram-negative bacterium Pseudomonas aeruginosa, respectively, induce multiple damage in spermatozoa. A reduction in the motility of spermatozoa coincided in a dose-dependent manner with apoptosis and necrosis at concentrations which were nondeleterious for dendritic cell-like immune cells. Moreover, sublethal doses of both signaling molecules induced premature loss of the acrosome, a cap-like structure of the sperm head which is essential for fertilization. Addressing their mechanism of action, we found that the bacterial molecule, but not the fungal molecule, actively induced the acrosome reaction via a calcium-dependent mechanism. This work uncovers a new facet in the interaction of microorganisms with human gametes and suggests a putative link between microbial communication systems and host infertility.

A polymorphism-specific "memory" mechanism in the ?(2)-adrenergic receptor.

Variant forms of the β2-adrenergic receptor found in different individuals show distinct responses to repeated drug exposure. Receptor Memory Drugs that activate the β2-adrenergic receptor (β2AR), or β2AR agonists, are used to treat various conditions, such as asthma and premature labor contractions. Frequently occurring polymorphisms that result in amino acid substitutions at position 16 in the β2AR have been correlated to different responses to these drugs. Ahles et al. (see also the Perspective by Insel) found that the β2AR responded differently to repeated drug stimulation, a phenomenon the authors call receptor “memory.” A variant of the β2AR with arginine at position 16 was slower in response to repeated stimulation. In contrast, a polymorphic variant of β2AR with glycine at position 16 showed faster activation when repeatedly stimulated, an effect that was associated with increased production of a downstream signaling molecule. The authors propose that these polymorphism-specific responses of the β2AR to continued stimulation may contribute to individual variation in responses to β2AR agonists. Signaling through G protein (heterotrimeric guanosine triphosphate–binding protein)–coupled receptors is affected by polymorphisms in receptor-encoding genes. Using fluorescence resonance energy transfer, we found that the β2-adrenergic receptor (β2AR) responded to repeated activation with altered activation kinetics. Polymorphic variants of the β2AR displayed divergent changes of β2AR activation kinetics that closely mimicked their different efficacies to generate cyclic adenosine 3′,5′-monophosphate. More efficacious variants became faster in their activation kinetics, whereas less efficacious variants became slower, compared to their initial activation. These differences depended on phosphorylation of the receptor by G protein–coupled receptor kinases. Our findings suggest an intrinsic, polymorphism-specific property of the β2AR that alters activation kinetics upon continued stimulation and that may account for individual drug responses.

Antigen‐presenting Cells in Pregnant and Non‐pregnant Human Myometrium

Citation Ivanisevic M, Segerer S, Rieger L, Kapp M, Dietl J, Kämmerer U, Frambach T. Antigen‐presenting cells in pregnant and non‐pregnant human myometrium. Am J Reprod Immunol 2010; 64: 188–196

Seminal plasma protects human spermatozoa and pathogenic yeasts from capture by dendritic cells

BACKGROUND During the process of fertilization, human spermatozoa are confronted with phagocytic cells of the female reproductive tract. Part of this host mucosal barrier are immature dendritic cells (DCs), which play an important role in the defense of invading microbial pathogens. In the present study, we investigated the potential interaction of spermatozoa with DCs and raised the question of whether seminal plasma impacts the interaction of DCs with spermatozoa or pathogenic microbes. METHODS AND RESULTS Flow cytometry and microscopy detected a strong association between spermatozoa and human monocyte-derived DCs, which was partly mediated by the DC-specific adhesion receptor, DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN). Coincubation assays also showed that capture of spermatozoa by DCs was blocked in the presence of increasing concentrations of seminal plasma. This inhibitory effect of seminal plasma was accompanied by altered DC maturation, revealed by flow cytometry analysis of maturation-specific DC surface markers. Phalloidin-staining of the DC cytoskeleton further visualized an impact of seminal plasma on DC morphology. To elucidate the molecular nature of the inhibitory activity of seminal plasma on sperm-DC -association, binding assays were performed in the presence of individual seminal plasma components. This approach identified specific prostaglandins-in particular, PGE₁, 19-OH-PGE₁ and PGE₂, which are present in seminal plasma at high concentrations-as likely inhibitory factors. In contrast to glass beads, the yeast Candida albicans, a common commensal organism and frequent pathogen of the genital tract, was also found to be protected from capture by DCs in the presence of seminal plasma or the specific prostaglandins. CONCLUSIONS The immunomodulatory power of seminal plasma may help spermatozoa to circumvent the attack of DCs of the female reproductive tract, thereby supporting successful fertilization. At the same time, however, such protective effects of seminal plasma may also modulate DC action during host-pathogen interactions.

Combination of gonadotropin-releasing hormone (GnRH) agonists with GnRH antagonists before chemotherapy reduce but does not completely prevent a follicle-stimulating hormone flare-up

Increasing evidence supports GnRH agonists to be an effective treatment to preserve ovarian function during chemotherapy, but the initial flare-up of FSH during the first week after GnRH agonist application still limits its use. The combination of GnRH agonists with GnRH antagonists might solve this problem to some extent as the addition of GnRH antagonists at least significantly reduces the FSH flare-up.

Termination of third-trimester pregnancy before term with gemeprost vaginal pessaries

Objective.  Determination of the efficacy and side‐effects of the synthetic prostaglandin analog gemeprost for termination of pregnancy in the third trimester.

Concept Paper on the Technique of Cryopreservation, Removal and Transplantation of Ovarian Tissue for Fertility Preservation

The cryopreservation of ovarian tissue with subsequent transplantation of the tissue represents an established method of fertility protection for female patients who have to undergo gonadotoxic therapy. The procedure can be performed at any point in the cycle and thus generally does not lead to any delay in oncological therapy. With the aid of this procedure, more than 130 births to date worldwide have been able to be recorded. The birth rate is currently approximately 30% and it can be assumed that this will increase through the further optimisation of the cryopreservation and surgical technique. The concept paper presented here is intended to provide guidance for managing cryopreservation and transplantation of ovarian tissue to German-speaking reproductive medicine centres.