The role of fertility preservation in patients with endometriosis.

Patients affected with severe endometriosis are at significant risk for ovarian tissue damage, which may lead to infertility, reduced response to ovarian stimulation, and occasionally, premature ovarian failure. The risk for a compromised ovarian reserve in young patients is especially high following repeated surgical intervention and in the presence of bilateral endometriomas. In many cases, enhanced loss of ovarian reserve may also result from the damaging effect of the pathologic process on follicle reservoir even without surgical interventions. Women diagnosed with severe endometriosis and those designated for extensive ovarian surgical intervention are frequently not planning to conceive. In light of recent advances in fertility preservation techniques (FPT), such as oocytes and ovarian tissue freezing, as well as their increasing success rates, we critically evaluate the options for FPT in patients suffering from endometriosis. Personalized counseling should be offered to all patients with endometriosis taking into account age, extent of ovarian involvement, current ovarian reserve, previous and impending surgeries for endometriosis, along with current success rates and possible risks associated with FPT.

The combination of genetic variants of the FSHB and FSHR genes affects serum FSH in women of reproductive age.

STUDY QUESTION: What is the effect of FSHB-211G>T together with the FSHR 2039 A>G on serum FSH in women? SUMMARY ANSWER: Serum FSH levels are affected by the combination of genetic polymorphisms in FSHR and FSHB. WHAT IS KNOWN ALREADY: The relationship between SNPs of the FSHR gene and serum FSH has not been completely clarified. Genetic variants of the FSHB gene have been associated with variation in gene transcription and serum FSH levels in men. No data have been published on the effect of the FSHB-211G>T in women, alone or in combination with the FSHR 2039 A>G. STUDY DESIGN, SIZE, DURATION: This study was a prospective study including 193 healthy women of reproductive age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile and otherwise healthy eumenorrheic women (n = 193) with normal BMI and serum FSH levels were recruited for the study. In all women early follicular phase FSH and AMH were measured by commercial assays, and antral follicle count was measured by transvaginal ultrasound. Genomic DNA was purified from total peripheral blood and genotyping for the two SNPs was performed. MAIN RESULTS AND THE ROLE OF CHANCE: No significant gradients of increasing or decreasing Day 3 FSH across the FSHR 2039 (AA/AG/GG) and FSHB-211 (GG/GT/TT) genotypes, respectively, were observed. When women were stratified according to the FSHR 2039, and FSHB-211 genotypes a statistically significant reduction of d3 FSH was shown in the group of women with the FSHB-211 GT + TT/FSHR2039 AA genotype compared with the FSHB-211 GG/FSHR2039 GG genotype, hence confirming a possible additive effect of the different SNPs in FSHR and FSHB on regulating serum FSH. LIMITATIONS, REASONS FOR CAUTION: This finding requires an independent confirmation. However, it confirms the relationship between serum FSH and FSHB together with FSHR gene polymorphisms already reported in males. WIDER IMPLICATIONS OF THE FINDINGS: The knowledge of the FSHB/FSHR genotype combination is fundamental for the proper interpretation of serum FSH levels in women of reproductive age. STUDY FUNDING/COMPETING INTERESTS: Merck Serono supported the study in the form of a research grant for the laboratory session. None of the authors have any competing interest to declare.

New molecular markers for the evaluation of gamete quality.

PURPOSE: Only 30 % of IVF cycles result in a pregnancy, so that multiple embryos need to be replaced, per treatment cycle, to increase pregnancy rates, resulting in a multiple gestation rate of 25 %. The use of new markers in the gamete selection, could reduce the number of the oocytes to be fertilized and embryos to be produced, but the tools to evidence the gamete competence remain unavailable and more studies are needed to identify bio-markers to select the best oocyte and sperm to produce embryos with higher implantation potentiality. METHODS: To define oocyte competence, the apoptosis of the surrounding cumulus cells and the oxygen consumption rates for individual oocytes before fertilization seems to provide a non-invasive marker of oocyte competence and hence a quantitative assessment of the reproductive potential for the oocyte. The chromatin integrity seems to be used also as biological marker of sperm competence, together with the morphological evaluation of large vacuoles in the head. RESULTS: The apoptosis rate of cumulus cells lower than 25 % and an higher oxygen consumption could be an evidence of an overall metabolic activity, related to a better fertilization ability and embryo cleavage quality. The apoptosis rate of the sperm chromatin, evaluated by direct Tunel in situ analysis, seems to be, also for the male gamete, a marker of competence and implantation potentiality, in particular when it is lower than 20 %. The evaluation of the presence of large vacuoles in the sperm head prior to perform ICSI seems to increase the implantation rate, but it is not associated to chromatin integrity. CONCLUSIONS: The biological concept of competence appears unrelated to any morphological parameters, so that it is necessary to investigate new molecular markers in the gamete selection. Apoptosis of cumulus cells in the oocytes and spermatozoa, revealing the presence of large vacuoles, could help to determine the competence of the gamete to be fertilize.

Intravenous aspirin (lysine acetylsalicylate) in the inpatient management of headache.

BACKGROUND: IV lysine acetylsalicylate (aspirin) has been shown to be effective in the treatment of acute migraine attacks, but little is known about its effectiveness and safety in patients hospitalized for management of severe headache, typically arising from abrupt withdrawal of other acute attack medications. METHODS: We present an audit of our use of IV aspirin in 168 patients in a tertiary referral setting. RESULTS: The findings demonstrate subjective approval of this medication by the patients and objective improvements in pain scores, a decrease of ≥3 points on a 10-point visual analog pain scale being seen on >25% occasions on which the medication was administered. Further, side effect rates were low (5.9%), with no serious adverse events. CONCLUSION: IV aspirin is safe, effective, and useful in the inpatient management of headache.

Unilateral photophobia or phonophobia in migraine compared with trigeminal autonomic cephalalgias.

Our objective was to compare the presence of self-reported unilateral photophobia or phonophobia, or both, during headache attacks comparing patients with trigeminal autonomic cephalalgias (TACs)--including cluster headache, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and paroxysmal hemicrania--or hemicrania continua, and other headache types. We conducted a prospective study in patients attending a referral out-patient clinic over 5 months and those admitted for an intramuscular indomethacin test. Two hundred and six patients were included. In episodic migraine patients, two of 54 (4%) reported unilateral photophobia or phonophobia, or both. In chronic migraine patients, six of 48 (13%) complained of unilateral photophobia or phonophobia, or both, whereas none of the 24 patients with medication-overuse headache reported these unilateral symptoms, although these patients all had clinical symptoms suggesting the diagnosis of migraine. Only three of 22 patients (14%) suffering from new daily persistent headache (NDPH) experienced unilateral photophobia or phonophobia. In chronic cluster headache 10 of 21 patients (48%) had unilateral photophobia or phonophobia, or both, and this symptom appeared in four of five patients (80%) with episodic cluster headache. Unilateral photophobia or phonophobia, or both, were reported by six of 11 patients (55%) with hemicrania continua, five of nine (56%) with SUNCT, and four of six (67%) with chronic paroxysmal hemicrania. Unilateral phonophobia or photophobia, or both, are more frequent in TACs and hemicrania continua than in migraine and NDPH. The presence of these unilateral symptoms may be clinically useful in the differential diagnosis of primary headaches.

Psychiatric side effects during methysergide treatment.

A patient is reported with psychological change characterised by impaired concentration and thought projection, followed by both severe anxiety and depression, starting after three weeks on high dose methysergide. The acute problem settled slowly after methysergide withdrawal and is likely to represent an unusual and serious side effect of that drug.

Age and homocysteine plasma levels are risk factors for thrombotic complications after ovarian stimulation.

BACKGROUND: The magnitude of thrombotic risk during ovarian stimulation cycles is not known. We calculated the magnitude of thrombotic risk in a cohort of women starting a new cycle of ovarian stimulation and investigated the role of inherited and acquired thrombophilia for these events. METHODS: This is an observational study involving outpatients of a clinical research centre. Consecutive women undergoing ovarian stimulation (n = 305) were enrolled. Blood samples for studying inherited and acquired thrombophilia were obtained > or = 2 months after the last cycle of treatment. Odds ratios (OR) and confidence intervals (CI) were determined for markers significantly associated with thrombotic events. Blood samples were analysed for inherited and acquired causes of thrombophilia (antithrombin, protein C, protein S, antiphospholipid antibodies, the Factor V Leiden and FIIA20210 mutations, the TT677 MTHFR genotype, and homocysteine plasma levels). RESULTS: Thrombotic events were observed in 4/747 cycles of ovarian stimulation, with a prevalence of 0.5%, corresponding to 1.6 per 100 000 cycles/woman. Age > or = 39 years and homocysteine plasma levels above the 97.5 percentile were significantly associated with thrombotic events during IVF [OR 15.2 (95% CI 2.0-115.0) and 14.4 (1.5-141.3) respectively]. CONCLUSIONS: Age > or = 39 years and mild hyperhomocysteinaemia are strongly associated with the occurrence of thrombotic events during IVF.

Ovarian function following radiation and chemotherapy for cancer.

High-dose chemotherapy and radiotherapy have increased the long-term survival of young patients with cancer; nevertheless, the toxic effects on ovarian function causing amenorrhoea, premature menopause and infertility, are still severe.

Total laparoscopic hysterectomy versus total abdominal hysterectomy: an assessment of the learning curve in a prospective randomized study.

The present randomized study was undertaken in order to compare the short-term results between total laparoscopic hysterectomy and abdominal hysterectomy in a centre with experience in laparoscopic surgery. From January 1997 to September 1998 inclusive, 102 women aged 44-71 years were randomly assigned to either total laparoscopic hysterectomy (n = 51 patients) or abdominal hysterectomy (n = 51 patients). The patients' demographic characteristics were similar in both groups. Average intra-operative blood loss was lower in laparoscopic hysterectomy than in abdominal hysterectomy (P

Endoscopic management of a case of 'complete septate uterus with unilateral haematometra'.

Endoscopy and ultrasound was used to diagnose a 13 year old virgin girl who presented with dysmenorrhoea and suspected right side adnexal tumescence. The girl was found to have a complete septate uterus with non-communicating right hemicavity and haematometra, an exceptional type of Müllerian anomaly. After pretreatment with buserelin, hysteroscopic metroplasty was successfully performed.

Activation of the acrosome reaction after treatment with human follicular fluid. A morphofunctional evaluation useful for in vitro fertilization.

Studies aided by transmission electron microscopy were made in order to evaluate the occurrence and efficiency of the human follicular fluid in the activation of the processes leading to the acrosome reaction; quantitative, qualitative and morphological data and relative evaluations are here presented. The effects of the human follicular fluid were compared with those determined by other types of treatment, semen untreated, Pellet-Swim-up, and Centrifugation on Discontinuous Percoll Gradient. The transmission electron microscope observations permitted to evaluate the percentage of sperm with an activation of the acrosome reaction in the different groups. The analysis of the data showed a statistically relevant difference (P < 0.001) among the first group (Control group) and the SU group, the MP group and the hFF group, regarding the sperm with AR activation. The sperm treatment with 50% diluted hFF represents an important option to the preparation protocols of the semen samples useful for ART.

Short-term use of Goserelin depot in the treatment of dysfunctional uterine bleeding.

UNLABELLED: STUDY-PLAN: an open study aimed at evaluating the results of a short term therapy (3 months) with Goserelin depot as a medical treatment of premenopausal dysfunctional uterine bleeding. PATIENTS: 60 premenopausal women (aged 36-50) with dysfunctional uterine bleeding, presenting simple endometrial hyperplasia. RESULTS: after the treatment, spontaneous menstrual bleeding recurred in 57/60 patients, while 3/60 (5%) patients remained amenorrheal during the whole period of follow-up, showing a postmenopausal hormonal pattern. In the first post-therapy menstrual cycle all the 57 patients had a bleeding score < 100; patients relapsing during the second, third and fourth cycle were respectively 2/54 (3.7%), 5/48 (10.7%) and 17/38 (44.7%). The fourth post-therapy cycle was delayed 6-9 months after the last injection of Goserelin. Both the mean blood loss and the mean duration of bleeding were significantly reduced in all post-therapy cycles. Eleven patients were anaemic before therapy (Hb < 12 g%); Goserelin treatment resulted in a normalization of the hematological parameters. At the end of treatment a small area of hyperplasia persisted in only 4/60 patients (6.7%). Localised or diffused hyperplasia were found respectively in 5/54 (9.3%) and in 1/54 patients (1.9%) at three months, and in 5/48 (10.4%) and 4/48 (8.3%) at a six-month follow-up. Side effects were infrequent. CONCLUSIONS: the long symptom-free period and the low incidence of side effects indicates Goserelin depot as a valuable medical treatment for dysfunctional uterine bleeding.

Assisted conception and immunological infertility.

Our work with a group involved in Assisted Conception (AC) has provided us with a perfect opportunity for making an assessment of the efficiency of the techniques used for the treatment of Male Antisperm Autoimmunization (MAA) and Female Antisperm Isoimmunization (FAI). The aim of this study is to present all the most important methods of AC used by our group for the treatment of immunological infertility, such as intrauterine insemination, intraperitoneal insemination, intrafallopian gamete transfer, in-vitro insemination and intrauterine embryo transfer, intrafallopian zygote transfer, intrafallopian embryo transfer, and gamete micromanipulation. In-vitro fecundation would appear to be particularly efficient in cases of FAI, while MAA would seem to benefit more from the use of gamete micromanipulation.

Computer-assisted assessment of the variations of sperm kinetics after semen treatment with Pellet Swim-up (PSu), and with centrifugation on a discontinuous Percoll gradient at reduced volumes (mini-CDPG).

The semen of the male partners of 37 infertile couples was analyzed with the use of the HTM-S Motility Analyzer (HTM-S MA). For each sample it was thus possible to assess the Total Concentration (TC), the Motile Cell Population Concentration (MCPC), the Progressive Cell Population Concentration (PCPC), the Average Path Velocity (VAP), the Straight Line Velocity (VSL), the Curvilinear Velocity (VCL), the Straightness (STR), the Linearity (LIN), the Lateral Head Displacement (ALH) and the Head Size (HS). The same parameters were then measured on the same semen after treatment with the Pellet Swim-up (PSu) and following Centrifugation on reduced-volume Discontinuous Percoll gradient (mini-CDPG). There was a significant difference in the TC (51.63 M/ml +/- 43.99 in the untreated ejaculate, 11.48 M/ml +/- 9.66 after PSu, 7.94 M/ml +/- 7.3 after mini-CDPG; chi r2 = 50.392, p < 0.05), in the MCPC (20.95 M/ml +/- 26.29 in the untreated ejaculate, 3.79 M/ml +/- 4.26 after PSu, and 2.74 M/ml +/- 3.73 after mini-CDPG; chi r2 = 33.55, p < 0.05), and in the PCPC (7.8 M/ml +/- 12.87 in the untreated ejaculate, 1.81 M/ml +/- 2.36 after PSu, and 1.28 M/ml +/- 1.73 after min-CDPG; chi r2 = 6.38; p < 0.05). The overall comparison between the couples showed a significant difference in the MCPC after PSu and after mini-CDPG (z = -2.09, p < 0.05) whereas no significant difference was found in the comparison off the results of either the TC after PSu and after mini-CDPG (z = -1.9; NS), or of the PCPC after PSu and after mini-CDPG (z = -1.68; NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Advantages of treatment with human follicular fluid in the management of severely dyspermic patients in human in vitro fertilization programs.

In 26 couples undergoing in-vitro fertilization and embryo transfer (IVF/ET), where the male partner was severely dyspermic, the seminal fluid was treated with Pellet Swim-up (PSu), modified by a 20-minute sperm incubation period in non-decomplemented human follicular fluid (hFF) diluted to 50%. In another group of 26 severely dyspermic couples undergoing IVF/ET, the semen was treated with a variant of centrifugation on discontinuous Percoll gradients (CDPG), called mini-CDPG. Pre-treatment with hFF produced a significant increase in oocyte fertilization rate (46.8% in the hFF group compared with 18.4% in the mini-CDPG couples; Kolmogorov-Smirnov Test: D = 0.5, p < 0.01), in the transfer rate per patient (96.1% in the hFF group and 50% in the mini-CDPG group; (Chi-square Test: x2 = 11.827, p < 0.001), and in the pregnancy rate per patient (respectively of 26.9% and 0%; Fisher's exact probability test: P = 0.0049, p < 0.01). There was a high miscarriage rate in the pregnancies obtained in the hFF group (42.8%). The results might be linked to a positive effect of the hFF on sperm capacity and on acrosome reaction. The Authors conclude that the use of hFF would seem to be an extremely useful treatment of the semen of severely dyspermic patients in assisted fertilization programs.