Combined down-regulation by aromatase inhibitor and GnRH-agonist in IVF patients with endometriomas-A pilot study.

OBJECTIVE: The key enzyme in the biosynthesis of estradiol, aromatase, has been demonstrated within endometriosis. Combined administration of aromatase inhibitor and GnRH-agonist may efficiently suppress estrogen biosynthesis through a combined pituitary, ovarian, peripheral and "in situ" action. The aim of this study was to test the concept of combined down-regulation prior to IVF in patients with endometriomas. STUDY DESIGN: Prospective pilot study in a university-based tertiary fertility clinic including 20 infertile patients with endometriomas undergoing IVF/ICSI. The patients received goserelin 3.6mg sc on treatment Days 1, 28 and 56, and one daily tablet of anastrozole 1mg from Day 1 to Day 69. Controlled ovarian stimulation was initiated from Day 70. Outcome measures were change in endometriomal volume and serum CA125 during down-regulation, standard IVF parameters including pregnancy and delivery rate, and endocrine response. The paired T test and Wilcoxon Signed Rank test were used to analyse paired differences. RESULTS: During the combined down-regulation, the endometriomal volume and the serum CA125 level decreased by 29% (3-39%) and 61% (21-74%), respectively (median (95%CI), P=0.007 and P=0.001). In the IVF/ICSI cycle, the number of oocytes retrieved was 7.5 (6.0-10.0) and the fertilization rate was 0.78 (0.38-1.0). Nine patients (45%) conceived, five (25%) had a clinical pregnancy, and three (15%) delivered healthy children (two singletons and one twin). CONCLUSIONS: Prolonged combined anastrozole and goserelin down-regulation significantly reduces endometriomal volume and serum CA125, and is compatible with IVF pregnancy and delivery. However, a high pregnancy loss was noted.

Assisted reproduction in male cancer survivors: fertility treatment and outcome in 67 couples.

BACKGROUND: Many male cancer survivors experience fertility problems due to antineoplastic treatment. We report the fertility outcome in 67 couples referred to assisted reproduction treatment (ART) because of male factor infertility due to cancer. METHODS: This was a retrospective study assessing the following parameters: diagnosis, cancer treatment, type of fertility treatment and type of sperm used, number of pregnancies and pregnancy outcome. RESULTS: Testicular cancer and lymphomas were the most prevalent diagnoses. Adjuvant treatment with chemo- and/or radiation therapy had been given to 90% of the men. Semen was cryopreserved in 82% of the men prior to treatment. Following antineoplastic treatment, 43% of the men had motile spermatozoa in the ejaculate, but 57% were azoospermic. A total of 151 ART cycles were performed [55 intra-uterine insemination (IUI), 82 ICSI and 14 ICSI-frozen embryo replacement (FER)]. The clinical pregnancy rate per cycle was 14.8% after IUI, 38.6% after ICSI and 25% after ICSI-FER. The corresponding delivery rates were 11.1, 30.5 and 21%. Cryopreserved semen was used in 58% of the pregnancies. The delivery rate per cycle was similar after use of fresh or cryopreserved spermatozoa. CONCLUSIONS: Male cancer survivors have a good chance of fathering a child by using either fresh ejaculated sperm or cryopreserved sperm.

Processing of seminal plasma hCAP-18 to ALL-38 by gastricsin: a novel mechanism of generating antimicrobial peptides in vagina.

The human cathelicidin, hCAP-18, is expressed both in neutrophils and in epithelial cells. hCAP-18 is processed to the antimicrobial peptide LL-37 by proteinase 3 in neutrophils. hCAP-18 is highly expressed in the epididymis with a subsequent high concentration in seminal plasma where the protein is present in its unprocessed and antimicrobially inactive form. We report here that hCAP-18 in seminal plasma is processed to generate a 38-amino acid antimicrobial peptide ALL-38 by the prostate-derived protease gastricsin when incubated at a pH corresponding to the vaginal pH. In accordance with this, seminal plasma derived hCAP-18 was found in its processed form in the vagina following sexual intercourse. The antimicrobial activity of ALL-38 against a variety of microorganisms tested is equal to that of LL-37. This enzymatic activation of a proantimicrobial substance in seminal plasma following exposure to the vaginal milieu represents a novel mechanism to prevent infection following sexual intercourse.

Biochemical evaluation of endometrial function at the time of implantation.

OBJECTIVE: To review the literature on various endometrial factors assumed to be of importance to implantation and to evaluate their potential clinical value in the assessment of endometrial function at the time of implantation in infertile women in natural and stimulated cycles. DESIGN: Literature review. RESULT(S): Cytokines such as leukemia inhibitory factor, colony-stimulating factor-1, and interleukin-1 have all been shown to play important roles in the cascade of events that leads to implantation. They participate in a synchronized cooperation between the endometrium and the preimplanting embryo under the influence of steroid hormones. The same applies to the integrin alpha(v)beta(3), glycodelin, and the polymorphic mucin 1. The usefulness of these factors to assess endometrial receptivity and to estimate the prognosis for pregnancy in natural and artificial cycles remains to be proven. CONCLUSION(S): The studies performed to date have mostly included only small groups of patients with a lack of fertile controls, and only a few prospective, controlled trials have been carried out. Therefore, definite conclusions about the clinical value of these factors in the assessment of endometrial function and prognosis for pregnancy after artificial reproductive therapy cannot be drawn at present. Further evaluation of their importance for and function during implantation is needed.