Daniela Mele

Effects of tibolone on the breast

OBJECTIVE to evaluate the effect of hormone replacement therapy and tibolone on the breast. STUDY DESIGN prospective, controlled, randomized study. SETTING Outpatient Menopause Clinic of the Second University of Naples. PARTICIPANTS forty four women in spontaneous menopause without any risk factor for breast cancer were randomly allocated to three groups: 15 patients (group A) were treated with transdermal oestrogens 50 microg, 2 patches/week for 3 weeks per month, plus acetate nomegestrolo per os 5 mg/die for 12 days per cycle, 17 patients (group B) were treated with tibolone 2.5 mg/die. Twelve patients not given any medication represented the control group (group C). METHODS at the time of recruitment and after at least 12 months of therapy the patients were subjected to a questionnaire aimed at quantifying the slight, moderate or severe presence of the tension/mastodynia symptoms and to a mammographic test to assess the parenchymal pattern according to a quantitative method: type 1 (less than 25% of mammary gland covered by dense tissue), type 2 (from 25% to 75% of total glandular area covered by dense tissue), type 3 (more than 75% of mammary parenchyma covered by dense tissue). Statistical analysis was carried out by means of Fishers exact test. RESULTS after at least 12 months of treatment in Group A 5 out of 15 patients (33%) showed a trend of increase in mammographic density not statistically significant (P=0.22) when compared with group B in which one patient showed a swift from type 1 to type 2 and another from type 2 to type 3. The analysis of tension/mastodynia symptoms revealed a significantly difference between the two groups (P=0.02): in group A mastodynia appeared in three previously asymptomatic women and increased in five women, with a total increase in the symptomatology in 8 out of 15 patients (53.3%), in group B only in one case (5%) mastodynia turned from slight to moderate. CONCLUSION in postmenopausal women oestroprogestogenic replacement therapy may be associated with an increase in mammographic density and with the onset or increase in mastodynia. On the contrary tibolone does not seem to affect normostructured mammas and may be considered a first-rate replacement therapy in case of mammas showing particular density or benign mastopathies.

Effects of a short-term suspension of hormone replacement therapy on mammographic density

OBJECTIVE To evaluate the effects of hormone replacement therapy (HRT) and of a short-term suspension of HRT on mammographic density. DESIGN Prospective clinical study. SETTING Outpatient menopausal clinic of the Second University of Naples. PATIENT(S) Ninety-seven healthy postmenopausal women. INTERVENTION(S) Thirty-nine menopausal women with intact uterus (group A) were treated with continuous transdermal E(2) plus acetate nomegestrolo sequentially added, 37 women in surgical menopause (group B) were treated with transdermal E(2) continuously administered, and 21 menopausal women did not receive any medication (group C). At the entry and after 12 months, a mammography was performed without suspension of HRT (group A1: 19 women; group B1: 19 women) or after a short-term suspension (group A2: 20 women; group B2: 18 women). MAIN OUTCOME MEASURE(S) Mammographic density evaluated according to a quantitative method. RESULT(S) At the second mammography, seven patients in group A1, four patients in group B1, and one patient in both groups A2 and B2 showed an increase in mammographic density, whereas no mammographic density increase was observed in patients in group C. A statistically significant difference in the mammographic density increase was found between group A1 and group A2; no difference was found between group B1 and B2. CONCLUSION(S) Suspension of HRT for about 3 weeks may reverse mammographic density increase associated with its use.

Recombinant Human FSH Reduces Sperm DNA Fragmentation in Men With Idiopathic Oligoasthenoteratozoospermia

A prospective randomized controlled study was designed to evaluate the effects of recombinant human follicle-stimulating hormone (rFSH) treatment on sperm DNA fragmentation in men with idiopathic oligoasthenoteratozoospermia (iOAT). One hundred twenty-nine men with sperm count less than 10 × 10(6) spermatozoa/mL and forward motility <25% were included; normal serum levels of FSH, luteinizing hormone (LH), and testosterone, and no other causes of infertility were enrolled. The patients were randomized into 2 groups: 65 men were treated on alternate days for 90 days with injections of 150 IU rFSH, and 64 subjects received nonantioxidant vitamin supplements. Main outcome measures were serum levels of FSH, LH, testosterone, and inhibin B and DNA fragmentation index (DFI) at baseline and after 90 days. No significant differences were observed between the 2 groups with regard to sperm parameters and hormone values. The DFI was similar between the 2 groups at the time of the enrollment but reduced significantly (P < .05) after rFSH therapy in study group, whereas no significant variation occurred in the control group. In the subgroup of patients with high basal DFI values (>15%), rFSH treatment significantly increased DFI (P < .01), whereas no significant variation occurred after 90 days of vitamin supplements. We conclude that rFSH administration improves sperm DNA integrity in iOAT men with increased DFI values. The degree of sperm DFI might be useful to identify those iOAT patients in which rFSH treatment can be advantageous.

Endometrial LGR7 expression during menstrual cycle

In a prospective observational study, 50 healthy patients aged 18-39 years, with regular ovulatory cycle and normal hormone levels, underwent endometrial biopsy in the proliferative and secretory phase of the menstrual cycle for semiquantitative reverse-transcription polymerase chain reaction analysis of mRNA for LGR7, the classic relaxin receptor. LGR7 is constitutively expressed in human endometrium, and an increased LGR7 immunostaining is demonstrated in the secretory phase, confirming the involvement of relaxin in the physiology of endometrium and suggesting its role in implantation.

Sequential protocol with urinary-FSH/recombinant-FSH versus standard protocol with recombinant-FSH in women of advanced age undergoing IVF

Abstract A stimulation protocol mimicking the physiological pattern of FSH release may improve IVF outcome in women of advanced age. Urinary-FSH delivers a wider range of isoforms including the most acidic produced during the early follicular phase when oestradiol level is low, a common condition in women of advanced reproductive age. We hypothesized that a stimulation protocol using urinary-FSH during the early follicular phase and then shifting toward recombinant-FSH may improve oocyte quality and pregnancy rate in 35–40 years old patients in IVF program. A retrospective study was performed: after a standard down-regulation with GnRH-analogue, 115 women underwent stimulation with urinary-FSH for 6 days according to a step-down approach and then shifting to recombinant-FSH (group A), 115 women underwent a stimulation protocol with only recombinant-FSH (group B). Days of stimulation were lower in group A than in group B, a higher proportion of MII oocytes and of grade 1 embryos, higher implantation rate and pregnancy rate were observed in group A versus group B. We conclude that a sequential protocol using urinary-FSH in the early days of stimulation and subsequently recombinant-FSH may improve the IVF outcome in patients of advanced reproductive age. Chinese abstract 刺激方案通过模拟人体内FSH释放的生理学特性可能会提高高龄妇女IVF的妊娠结局。尿源性FSH提供了更多的亚型，包括酸性最强的亚型，该亚型只在雌二醇水平很低的早卵泡期产生。这种情况在高生育年龄患者中常见。假设对30-40岁患者行IVF促排卵过程中早卵泡期应用尿源性FSH而后转为应用重组FSH，该方案可能会提高卵子质量和妊娠率。一项回顾性研究显示：通过标准的GnRH-a降调节方案，115名患者前6天接受尿源性FSH刺激而后转为重组FSH刺激（A组），另外115名患者仅接受重组FSH刺激方案（B组）。与B组相比，A组刺激天数更少、MII卵细胞和一级胚胎比例较多且有更高的移植率和妊娠率。因而我们得出结论：在早期应用尿源性FSH而后转用重组FSH刺激的序贯方案可以提高高龄妇女的IVF结局。

Seminal anti-Müllerian hormone levels during recombinant human follicle-stimulating hormone treatment in men with idiopathic infertility undergoing assisted reproduction cycles

A prospective study was designed to investigate the effects of recombinant human follicle‐stimulating hormone (rhFSH) on seminal anti‐Müllerian hormone (AMH) levels in men with idiopathic oligoasthenoteratozoospermia (iOAT), researching possible relationships between the seminal AMH behavior and the response to the treatment. Thirty‐nine men who were candidates for intracytoplasmic sperm injection (ICSI) because of iOAT were enrolled. Patients were treated on alternately days with 150 IU of rhFSH for at least 3 months before assisted reproduction cycles. Main outcome measures were seminal AMH concentrations before and after rhFSH therapy. After treatment, 16 subjects (responders) showed an improvement in their sperm count compared to baseline (7.6 ± 2.9 vs. 19.3 ± 7.7, p < 0.01) whereas 23 men (non‐responders) experienced no sperm modifications. Baseline seminal AMH concentrations were significantly higher in responders than in non‐responders (53.0 ± 30.6 vs. 34.6 ± 18.5, p < 0.025). Following therapy, a greater increase in AMH levels was observed in responders compared to non‐responders (Δ = 24.8 ± 36.4 vs. Δ = 6.4 ± 11.2, p < 0.028). Seminal AMH levels significantly and positively correlated with sperm count (after rhFSH treatment rho = 0.647, p < 0.001). Our study suggests that rhFSH improves sperm count in a quota of iOAT men, and the subjects who respond to the treatment have higher baseline seminal AMH concentrations than the patients who are not responsive. Seminal AMH could be helpful to select those infertile men who may benefit from rhFSH treatment.

Endometrial LGR7 expression and implantation failure.

Abstract Implantation failure is considered as a major cause of infertility in women with recurrent pregnancy loss (RPL) and in otherwise healthy women with unexplained infertility. Preliminary data in primates suggested that relaxin (RLX) is involved in endometrial preparation for implantation. In a prospective observational study, the endometrial RLX receptor (LGR7) expression was assessed in three groups of patients with regular ovulatory cycle and normal uterine cavity: 23 with RPL (Group A), 23 with unexplained infertility undergone at least three cycles of failed in vitro fertilization (IVF) reporting good oocyte and embryo quality (Group B), 23 with proven fertility (Group C). Assessment of LGR7 expression was performed with both polymerase chain reaction (PCR) analysis and immunohistochemistry on endometrial samples obtained with hysteroscopic biopsy performed in the secretory phase of the menstrual cycle. Endometrial LGR7 was less expressed in group A and B versus C, both by PCR analysis (p = 0.024) and immunohistochemistry. The decreased expression of the endometrial RLX receptor in women with implantation failures, both in vitro fertilization failure and recurrent pregnancy loss, suggests that RLX may play a crucial role in the structural and functional changes of the endometrium during the window of implantation.