Ovarian Stimulation Protocol in IVF: An Up-to-Date Review of the Literature.

The Assisted Reproductive Technology (ART) was born in order to help couples with infertility issues in having a baby. The first treatments of IVF used the spontaneous cycle of the women, with the retrieval of only one oocyte. Further studies have shown that it is possible to induce ovulation by administrating gonadotropins during the menstrual cycle, in order to obtain a higher number of oocytes. Many stimulation protocols have been introduced for controlled ovarian hyperstimulation of patients undergoing in vitro fertilization treatment. This review describe the different stimulation protocols using follicle-stimulating hormone (FSH) in combination with Gonadotropin releasing hormone (GnRH) either agonist or antagonist, oral supplementations and ovarian triggering. Using GnRH antagonist protocols have been demonstrated to improve significantly the clinical pregnancy rates for expected poor and high-responders, and in those women at high risk of developing ovarian hyperstimulation syndrome (OHSS). Two meta-analyses showed a better outcome in terms of the live birth rate when highly purified human menopausal gonadotropin (HMG) was used for ovarian stimulation compared with recombinant follicle stimulating hormone (rFSH) in the GnRH agonist long protocol. One of the most efficient stimulation protocol is the use of a combined protocol of human derived urinary FSH (uFSH) and rFSH. Combined protocol has resulted in a significant increase in the proportion of mature metaphase II oocytes and grade 1 embryos when compared to either rFSH or uFSH alone. A significantly higher delivery rate was achieved in rFSH+uFSH compared to the other protocols in poor and normal responders. Studying the combination of melatonin with myo-inositol and folic acid has also showed a higher percentage of mature oocytes in the melatonin group and a higher percentage of G1 embryos as well. However, It remains a crucial step to confirm the efficacy of such protocols for clinical application and it is still needs to comparison studies on larger scale with more focused on the differences in patients' response criteria and additional confounding variables, in order to draw more defined conclusions.

Fas and Fas-Ligand in Eutopic and Ectopic Endometrium of Women With Endometriosis: The Possible Immune Privilege of Ectopic Endometrium.

The Fas/Fas-Ligand system is an important mediator of apoptosis. We analyzed their expression in tissue specimens obtained from 33 women with severe endometriosis and 18 women without endometriosis. Immunostaining for Fas-Ligand in the eutopic endometrium was stronger in the epithelial cells of secretory phase, while the epithelial cells of endometriotic lesions showed a significantly stronger staining for Fas-Ligand independently from the menstrual phase (P < 0.01). Immunostaining for Fas in the eutopic endometrium showed a reduced staining during the proliferative phase, whereas it was strong in the secretory phase. The epithelial cells of the ectopic endometrium showed a reduced staining for Fas independently from the menstrual phase with respect to the eutopic tissue (P < 0.01). The reduced expression of Fas in the ectopic endometrium with the contemporary higher expression of Fas-Ligand in the corresponding cells suggests a possible immune privilege of this tissue.

Subsequent impaired fertility (with or without sperm worsening) in men who had fathered children after a left varicocelectomy: A novel population?

OBJECTIVES: The objective of this paper was to assess whether the beneficial effects of a varicocelectomy on fertility are transitory or definitive after a first fathering. MATERIALS AND METHODS: This was a retrospective study which involved seven andrological centers. The files of 2223 patients who underwent subinguinal ligation of a high grade left varicocele for (oligo)±(astheno)±(terato)-spermia and infertility between January 1(st), 2002 and January 1(st) 2013 were reviewed. Inclusion criteria for the patients were the following: Sperm count improvement and fathering a child after an uneventful left varicocelectomy; 745 patients were considered. Patients who had undergone three assessments for (in-) fertility: Before surgery, before the first fathering and after the first fathering were included in the study. Each assessment included: Clinical history, physical examination, two sperm analyses, bilateral scrotal Duplex scans, blood hormonal levels [follicle stimulating hormone (FSH), luteinising hormone (LH), testosterone (T) and prolactin (PRL)]. RESULTS: Forty patients were finally studied; they all had an improved sperm count and had fathered once after surgery. Fifteen had fathered twice and still had their sperm count increased after the second fathering. Twenty-five patients could not father twice; 13 patients had their sperm count decreased after the first fathering and 12 did not. A decrease in testicular volume and an increase in FSH paralleled the worsening of sperm concentration, motility and morphology after fathering. No other differences could be observed between the groups. CONCLUSIONS: Our data indicated that the beneficial effects of a varicocelectomy might be transitory in some cases.

Multivariate analysis to predict letrozole efficacy in improving sperm count of non-obstructive azoospermic and cryptozoospermic patients: a pilot study.

We tested the hypothesis that letrozole increases sperm count in non-obstructive azoospermic or cryptozoospermic patients with a testosterone (T)/17-beta-2-oestradiol (E2) ratio <10. Forty-six patients with no chromosomal aberrations were randomized into two groups: 22 received letrozole 2.5 mg per day for 6 months (Group 1: 6 azoospermic + 16 cryptozoospermic patients), while 24 received a placebo (Group 2: 5 azoospermic + 19 cryptozoospermic patients). The following data were collected: two semen analyses, clinical history, scrotal Duplex scans, body mass index (BMI), Y microdeletion, karyotype and cystic fibrosis screens and follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2, T and prolactin levels. Both before and after letrozole or placebo administration, the patients underwent two semen analyses and hormonal assessments. The differences were evaluated using the Mann-Whitney U test. The relationships between sperm concentration after letrozole administration with respect to FSH, T/E2 ratio, bilateral testicle volume and BMI before letrozole administration were assessed using multivariate analysis. The side effects were assessed using the chi-square test. Group 1 had sperm concentration (medians: 400-1.290 × 10(6) ml(-1); P<0.01) and motility (medians: class A from 2% to 15%; P<0.01), FSH, LH and T significantly increased, while Group 2 did not. E2 levels diminished significantly in Group 1, but not in Group 2. Eight patients in Group 1 demonstrated side effects, whereas no patient side effects were observed in Group 2. The sperm concentration after letrozole administration is inversely related to T/E2, FSH and BMI; a direct relationship emerged between sperm concentration and testicular volume.

Association between Peyronie disease and low serum testosterone levels: detection and therapeutic considerations.

The aim of this paper was to find a link between Peyronie disease (PD) and bioavailable testosterone (bT)/free testosterone (fT) blood levels. Subjects with no erectile dysfunction were prospectively studied with respect to 3 parameters: differences in bT/fT between 106 PD patients and 99 healthy controls; differences in plaque area, penile curvature, and pain between 54 PD patients with low bT/fT and 52 PD patients with normal bT/fT; and differences in intraplaque verapamil efficacy between 20 hypogonadal PD patients supplemented with testosterone and 23 hypogonadal PD patients administered a placebo. Medical history, objective examination, and dynamic duplex scanning of the penis, both before and 8 months after the end of the therapy (ie, at the end of the study period), were used to assess PD. Testosterone supplementation was carried out with testosterone buccal adhesive patches 2 × 30 mg/d for the entire study period. bT and fT were significantly lower in PD patients than in control patients. The plaque area was significantly higher in PD patients with low bT/fT than in patients with normal bT/fT. No significant difference emerged when pain or penile deformity were examined. Plaque area and penile curvature improved to a greater extent when intraplaque verapamil injections were associated with testosterone administration than when associated with a placebo. Men with PD had lower bT/fT than healthy controls. In these patients, supplementation with testosterone improved the efficacy of intraplaque verapamil. Plaque area and penile curvature were more severe in hypogonadal PD.

Preliminary study of letrozole use for improving spermatogenesis in non-obstructive azoospermia patients with normal serum FSH.

We investigated whether letrozole (2.5 mg day(-1)) improves sperm count in non-obstructive azoospermia (NOA) patients. Four men were included in this study, and they had folliculo-stimulating hormone and other hormone levels within the normal range and no varicoceles or chromosomal aberrations. These four patients were administered letrozole for 3 months. Sperm count, testicular volume, gonadotropin, testosterone (T) and estradiol (E2) blood levels were assessed before, during and 1 week after the suspension of treatment. All patients showed spermatozoa in their ejaculate, increased gonadotropin and T levels and lower E2 levels (P<0.05 in all cases), when letrozole was administered. This suggests that letrozole treatment might improve sperm count in an NOA sub-population; however, more studies, including the proper controls, are needed to confirm its efficacy.

Cinnoxicam and L-carnitine/acetyl-L-carnitine treatment for idiopathic and varicocele-associated oligoasthenospermia.

The objective of this study was to detect a therapy for idiopathic and varicocele-associated oligoasthenospermia (OAT). Idiopathic and varicocele OAT patients were randomized into 3 groups. Each group was composed of varying degrees of left varicoceles (graded into 5 grades with echo-color Doppler) and of idiopathic OATs. Group 1 used a placebo, group 2 used oral L-carnitine (2 g/d) + acetyl-L-carnitine (1 g/d), group 3 used L-carnitine/acetyl-L-carnitine + 1 x 30-mg cinnoxicam suppository every 4 days. Drugs were administered for 6 months. The groups were composed as follows: group 1, 71 varicoceles and 47 idiopathic OATs; group 2, 62 varicoceles and 39 idiopathic OATs; group 3, 62 varicoceles and 44 idiopathic OATs. Sperm concentration, motility, and morphology before during and after treatments were assessed. Pregnancy rates and side effects were recorded. Group 1 did not have modified sperm patterns during treatment. Group 2 had significantly increased sperm patterns at 3 and 6 months into therapy in idiopathic patients and in patients with grades I, II, and III varicocele, but not in grades IV and V. Group 3 had significantly increased sperm parameters in all patients, with the exception of grade V varicocele. Group 3 sperm patterns proved significantly higher during therapy than group 2. All sperm patterns fell to baseline after therapy suspension. Minor side effects occurred. Pregnancy rates were 1.7% (group 1), 21.8% (group 2), and 38.0% (group 3) (P <.01). L-carnitine/acetyl-L-carnitine + cinnoxicam suppositories proved a reliable treatment for low-grade varicoceles and idiopathic OATs.

Dyspermia and testicular artery peak systolic velocity.

OBJECTIVE: To compare reliability of peak systolic velocity (PSV), end diastolic velocity (EDV), resistivity index (RI) of testicular arteries, folliculostimulating hormone (FSH) and testicular volume in the differential diagnosis of dyspermias. PATIENTS AND METHODS: Testicle volume, FSH, PSV, EDV, and RI were compared with analysis of variance among the following patients or controls: 9 obstructive azoospermic (OA), 20 non obstructive (NOA), 17 oligoasthenospermic varicoceles + male accessory glands inflammation (MAGI), 38 undetermined oligoasthenospermic, 19 MAGI, 11 varicoceles, 32 subjects with normal sperm analysis who recently fathered (fertile controls), and 15 subjects with normal sperm analysis with varicocele who recently fathered. RESULTS: Only PSV and RI proved to be selective for the different classes of patients, while EDV, FSH and testicle volume did not. Varicoceles, varicoceles + MAGI and fertile varicoceles showed the highest PSV and RI; fertile controls, OAs and MAGIs displayed similar PSV and RI; undetermined patients displayed significantly lower PSV and RI, NOAs' PSV and RI proved to be the lowest. CONCLUSIONS: RI and PSV proved to be a reliable tool to be routinely used in the clinical study of infertile/dyspermic males, whereas EDV, FSH and testicle volume did not.