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.

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.

Thanatophoric dysplasia in monozygotic twins discordant for cloverleaf skull: prenatal diagnosis, clinical and pathological findings.

We present male monozygotic twins with thanatophoric dysplasia (TD) type I concordant for long bone abnormalities and discordant for cloverleaf skull. The twins were the product of the second pregnancy of unrelated parents, with advanced paternal age. Prenatal diagnosis and postmortem examination showed severe rhizomelic shortness of limbs, bowing of the long bones with "telephone-receiver" femora in both twins, and cloverleaf skull and hydrocephalus in one of them. It is now accepted that most of cases of TD, such as in the present report, represent an autosomal dominant mutation with a high new mutations rate.

Role of leuprolide acetate depot in hysteroscopic surgery: a controlled study.

OBJECTIVE: To evaluate leuprolide acetate (LA) depot (Enantone Depot, Takeda, Italy) when administered preoperatively in hysteroscopic surgery. DESIGN: Prospective, comparative study. SETTING: University Clinic of Obstetrics and Gynecology. PATIENTS: One hundred ninety-three patients (114 pretreated with LA depot and 79 controls) who underwent hysteroscopic surgery for uterine septa (group A), submucous fibroids (group B), and abnormal uterine bleeding (group C). RESULTS: In groups B and C there was a significant reduction in the operating time, bleeding during the operation, and the amount of distention medium required after LA depot administration, but no significant differences in surgical feasibility or efficacy were found in group A patients after treatment. CONCLUSION: Preoperative treatment with LA depot is effective in making hysteroscopic surgery easier.

Initial experience of a new linear everting falloposcopy system in comparison with hysterosalpingography.

OBJECTIVE: To assess the endolumenal portion of the fallopian tube from ostium to fimbria using a specially designed linear everting catheter and microendoscope. The study compared falloposcopy results with those obtained with hysterosalpingography (HSG) in the same patients and explored the system's ability to classify internal tubal conditions. DESIGN: A prospective study of a new diagnostic technique, falloposcopy, versus conventional means of evaluating tubal status. SETTING: A tertiary university infertility center. PATIENTS: Eighteen infertile patients with a previous history of infertility of at least 2 years duration. INTERVENTION: Diagnostic falloposcopy was performed on a total of 31 tubes. RESULTS: Although the results of HSG and falloposcopy were in agreement in 19 cases, falloposcopy findings were at significant variance with HSG in 12 cases (40%). Seventeen of the tubes visualized by falloposcopy were considered to be normal, 10 showed mild disease, and 4 were severely damaged. CONCLUSION: Falloposcopy using the linear everting catheter is rapid and atraumatic. It provides more complete information concerning tubal status than HSG and as such constitutes an important advance in diagnosis and therapy planning.

Concomitant gonadotropin-releasing hormone agonist and menotropin treatment for the synchronized induction of multiple follicles.

In an effort to overcome possible interference by endogenous gonadotropin-ovarian hormone dynamics, desensitization of the pituitary gonadotropins by a gonadotropin-releasing hormone agonist (GnRHa) was achieved in 12 women with repeatedly failed attempts at multiple follicular stimulation. Eight women were scheduled for in vitro fertilization (IVF) and embryo transfer (ET), and 4 for gamete intrafallopian transfer (GIFT). Stimulation failure was characterized by premature luteinization, poor estradiol (E2) response, or inadequate follicular growth. The agonist was administered by nasal spray 500 to 600 micrograms/day beginning on days 21 to 23 of the menstrual cycle. A rapid desensitization occurred by 7.6 +/- 0.6 days (mean +/- standard error [SE]) following the initial dose. Gonadotropin stimulation was begun when pituitary and ovarian suppression was judged to be adequate. In response to gonadotropin stimulation, a continuous rise of E2 was observed in all patients with a mean of 989 +/- 46 pg/ml on the day of hCG. A cohort of synchronized follicles was recruited and matured. The mean number of growing follicles per patient was significantly higher (P less than 0.0001) in combined therapy than in previously failed cycles (8.0 +/- 0.3 versus 3.2 +/- 0.1). All the patients underwent oocyte retrieval and 94.3% of the harvested oocytes were preovulatory. A high fertilization rate (89.7%) of the inseminated oocytes occurred in IVF patients.

Gamete intrafallopian transfer in the treatment of infertility: the first series at the University of Palermo.

Twenty-six couples with unexplained infertility (UI), nine women with repeated failures of artificial insemination with donor semen (AID), three women with mild endometriosis, three with periadnexal adhesions, one with hostile (not immunologic) cervical mucus, and one couple in which the male partner was affected by asthenospermia were treated by the gamete intrafallopian transfer (GIFT) technique. Three different protocols for controlled ovarian hyperstimulation were used, and an adequate follicular growth and oocyte maturation were achieved in all cases. Seventeen pregnancies were obtained, for a global pregnancy rate of 38.6%. Two pregnancies (11.7%) ended in clinical abortions, and one (5.8%) was a tubal pregnancy. Of the ongoing pregnancies, one is twin and two are triplets. Seven pregnancies (six ongoing, one abortion) were obtained in the UI group (26%), six (all ongoing) in the failed AID group (66.6%), two continuing pregnancies in the three patients with endometriosis (66.6%); the tubal pregnancy and one clinical abortion occurred in the group with adnexal adhesions. No pregnancies were obtained in the patient with hostile cervical mucus and in the couple with infertility presumably due to poor semen. These encouraging results and the simplicity of the technique suggest that GIFT could be an effective approach that could be programmed during a well-timed laparoscopy where persistent infertility exists in association with apparently normal fallopian tubes.

Successful gamete intrafallopian transfer following failed artificial insemination by donor: evidence for a defect in gamete transport?

Gamete intrafallopian transfer (GIFT) was offered as an alternative treatment to 48 women who failed to conceive after artificial insemination with donor semen (AID) in numerous attempts (9 to 24 cycles). The evaluation of these women showed no major cause of infertility as evidenced by normal endocrine, cervical, uterine, and tubal factor studies. Their partners were either azoospermic or severely oligoasthenospermic. During the GIFT cycle, follicular development was induced with (1) clomiphene citrate (days 3 to 7) plus human menopausal gonadotropins (hMG) from day 6 on or (2) human follicle-stimulating hormone (days 3 to 4) plus hMG (day 5 on), until ultrasound revealed 2 follicles 16 mm and serum estradiol (E2) was greater than 700 pg/ml. Human chorionic gonadotropin (hCG) 10,000 IU was administered, and 36 hours later follicular aspiration was performed. One to three oocytes and 100,000 motile sperm were transferred to each fallopian tube through the fimbria via laparoscopy or minilaparotomy. Twenty-seven clinical pregnancies were achieved (56%) per GIFT cycle. Eight miscarriages occurred during the first trimester (29% of all pregnancies), whereas no ectopic pregnancies were observed. These data conclusively show the value of the GIFT procedure in the treatment of cases with failed AID.

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.

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.

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.