Awareness of the effects of postponing motherhood among hospital gynecologists: is their knowledge sufficient to offer appropriate help to patients?

PURPOSE: The aim of this study is to ascertain the awareness of hospital gynecologists about the effects of woman's age on spontaneous fecundity and on the efficacy of assisted reproduction techniques (ARTs). METHODS: One hundred fifty-six gynecologists working in public or private Italian hospitals, without specific experience in reproductive medicine and ART, were administered a multiple-choice answer questionnaire addressing (a) the effect of age on woman's spontaneous fecundity, (b) the tools to estimate the ovarian follicular reserve, and (c) the outcome of ART in women above 40 years. RESULTS: Approximately half of the interviewed gynecologists indicated the woman's age limit for successful reproduction between 44 and 50 years; fertility lifespan was believed to be prolonged by oral contraception, pro-fertility medical treatments, or ART. The correct meaning of serum FSH measurement was known by approximately one third of the interviewed doctors. The effectiveness of ART for women of advanced age was overestimated by half of the gynecologists, especially in case of patients having regular cycles and/or small follicles at ultrasound. CONCLUSIONS: Overall, the survey clearly showed that the knowledge of hospital gynecologists about the effects of age on woman's fertility and ART effectiveness is largely insufficient to offer scientifically correct, helpful information to patients. Properly targeted corrections to academic and periodical educational programs for Ob/Gyn specialists are warranted.

Efficacy and safety of late-start Corifollitropin-alfa administration for controlled ovarian hyperstimulation in IVF: a cohort, case-control study.

OBJECTIVE: To investigate efficacy and safety of a controlled ovarian stimulation (COS) protocol in which a single dose of Corifollitropin-alfa (CFα) was administered on day 4 of a GnRH-antagonist cycle. DESIGN: Cohort case-control study. SETTING: University Hospital. PATIENTS: One hundred twenty-two normally cycling women expected to be normal responders to COS. INTERVENTIONS: In 61 patients, CFα (100-150 µg) was injected subcutaneously on day 4 of a spontaneous menstrual cycle; a GnRH-antagonist was added from day 8 (fixed protocol; 0.25 mg/day). If needed to complete follicular maturation, recombinant FSH (rFSH) daily injections (150/200 IU/day) were given from day 11. A control group of 61 matched women was stimulated with daily subcutaneous injections of rFSH (100-150 U/day) from day 4 of the cycle, and received GnRH-antagonist (0.25 mg/day) from day 8. IVF or ICSI was performed according to the sperm characteristics, and 1-2 embryos were transferred in utero under US guidance on day 2. MAIN OUTCOME MEASURES: Number of retrieved cumulus-oocyte complexes (COCs), clinical pregnancy rate (PR), implantation rate (IR), ongoing PR at 10 weeks, number of injections/cycle, ovarian hyperstimulation syndrome (OHSS) rate. RESULTS: No cycle was cancelled and the mean number of retrieved COCs was comparable in patients and controls. About 60% of CF-alfa treated women had no need of daily rFSH addition, and the mean number of injections/cycle was significantly lower in the CF-alfa group than in controls (p < 0.05). The ongoing PR/transfer was 36.8% in CF-alfa group and 37.5% in controls. No patient developed severe OHSS, and the incidence of moderate OHSS was similar in cases and controls. CONCLUSIONS: CFα may be started on day 4 of the cycle obtaining results comparable to those of a COS using day 4-start daily rFSH, with significantly less injections and a similar risk of OHSS.

A slowly reabsorbed, echogenic surgical thread provides a long-lasting ultrasound-detectable marker of grafted ovarian tissue.

This communication reports a novel technical solution for the orthotopic transplant of cryostored-thawed ovarian tissue. The described technique was applied to three young women with iatrogenic ovarian failure. An echogenic thread that is reabsorbed after 6 months was used to fasten the thawed ovarian small fragments before grafting them onto the atrophic ovary. This technical solution made it possible to avoid the loss of small tissue pieces during laparoscopic grafting as well as to precisely localize the grafted tissue by transvaginal ultrasound during the following months. The precise localization of the grafted tissue was particularly helpful when its revascularization and functional recovery were followed up using, respectively, colour Doppler and transvaginal follicle growth examination. In conclusion, the use of a slowly reabsorbed, ultrasound-detectable surgical thread as an ultrasound-detectable marker able to improve the localization of the exact site at which ovarian tissue was grafted is proposed.

Fertility preservation program before ovarotoxic oncostatic treatments: role of the psychological support in managing emotional aspects.

Fertility preservation programs (FPPs) based on oocyte or ovarian tissue cryostorage may be offered to women facing oncostatic treatments at risk of precocious ovarian insufficiency. The way in which FPPs are presented to patients affects their decision to join them. We studied herein 48 young women to whom a FPP was proposed, aiming at clarifying the emotional aspects involved. A psychologist attended the consultations in which the FPP was offered to patients; at the end of the talk, a questionnaire was administered and a semi-structured interview was carried out. Finally, the STAI test was administered to measure trait (TAI) and state (SAI) anxiety, both immediately after consultation, and later on, when patients returned home. We observed that the possibility to join a FPP implied important emotional aspects, and that the presence of a psychologist was helpful to integrate technical information and emotions as well as to reduce trait and state anxiety levels. Our study suggests that the presence of a psychologist during the meeting in which a FPP is offered improves communication between doctors and patients, and helps these women to get a full awareness before choosing to join the FPP.

MILD ovarian stimulation with GnRH-antagonist vs. long protocol with low dose FSH for non-PCO high responders undergoing IVF: a prospective, randomized study including thawing cycles.

OBJECTIVE: To compare the effectiveness of two stimulation protocols in non-polycystic ovary (PCO) high responders undergoing in vitro fertilization (IVF). DESIGN: Prospective randomized trial. SETTING: A Reproductive Medicine and IVF Unit of a University Hospital and a private IVF Clinic. METHODS: Four hundred-and-twelve normoovulatory women with good ovarian responsiveness were randomized to receive either the "mild" (FSH 150 IU/day from day 4 of a spontaneous cycle followed by GnRH-antagonist from day 8; n = 205) or the "long" (FSH 150 IU/day; n = 207) stimulation protocol. The outcome of these two regimens was compared including "fresh" and thawing cycles. RESULTS: The total FSH dose and the peak estradiol level were significantly lower in the "mild" protocol, whereas the retrieved oocytes, fertilization rate, number and quality of embryos, pregnancy and implantation rates, cumulative "fresh plus thaw" success rate, and incidence of severe ovarian hyperstimulation syndrome were comparable with the two regimens. CONCLUSIONS: In young, normoovulatory patients with good ovarian responsiveness undergoing IVF the "mild" stimulation protocol has effectiveness and risks comparable to the "long" protocol with low FSH starting dose, even when thawing cycles are included in the comparison.

Milder is better? Advantages and disadvantages of "mild" ovarian stimulation for human in vitro fertilization.

In the last decades, several steps have been made aiming at rendering human IVF more successful on one side, more tolerable on the other side. The "mild" ovarian stimulation approach, in which a lower-than-average dose of exogenous gonadotropins is given and gonadotropin treatment is started from day 2 to 7 of the cycle, represents a significant step toward a more patient's friendly IVF. However, a clear view of its virtues and defects is still lacking, because only a few prospective randomized trials comparing "mild" vs. conventional stimulation exist, and they do not consider some important aspects, such as, e.g., thawing cycles. This review gives a complete panorama of the "mild" stimulation philosophy, showing its advantages vs. conventional ovarian stimulation, but also discussing its disadvantages. Both patients with a normal ovarian responsiveness to exogenous gonadotropins and women with a poor ovarian reserve are considered. Overall, we conclude that the level of evidence supporting the use of "mild" stimulation protocols is still rather poor, and further, properly powered prospective studies about "mild" treatment regimens are required.

Family planning, fertility awareness and knowledge about Italian legislation on assisted reproduction among Italian academic students.

Over the last century, most industrialized countries have experienced a progressive increase in maternal age at first pregnancy and a reduction of fertility rate, with important social and economic consequences. Moreover in Italy a very restrictive law on assisted reproductive technologies was introduced in 2004, limiting its effectiveness and causing a strong public debate that unfortunately focused more on the political and ethical implications of the law than on the medical and technical aspects of assisted reproduction. The present study performed an epidemiological investigation among the students of Turin University in the year 2006/07 in order to assess three aspects: the factors affecting the decision to become parents, their level of consciousness about human reproduction and their level of knowledge about the legal rules that regulate assisted reproduction in Italy. The study also wanted to clarify how the sex (male or female) and the type of education (sciences or humanities) could affect their opinions and knowledge in this area. It was observed that young people consider parenthood an important part of their life, but knowledge about human fertility and legal rules regulating assisted reproduction is rather poor, regardless of sex and type of education.

Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics.

The assessment of oocyte quality in human in vitro fertilization (IVF) is getting increasing attention from embryologists. Oocyte selection and the identification of the best oocytes, in fact, would help to limit embryo overproduction and to improve the results of oocyte cryostorage programs. Follicular fluid (FF) is easily available during oocyte pick-up and theorically represents an optimal source on non-invasive biochemical predictors of oocyte quality. Unfortunately, however, the studies aiming to find a good molecular predictor of oocyte quality in FF were not able to identify substances that could be used as reliable markers of oocyte competence to fertilization, embryo development and pregnancy. In the last years, a well definite trend toward passing from the research of single molecular markers to more complex techniques that study all metabolites of FF has been observed. The metabolomic approach is a powerful tool to study biochemical predictors of oocyte quality in FF, but its application in this area is still at the beginning. This review provides an overview of the current knowledge about the biochemical predictors of oocyte quality in FF, describing both the results coming from studies on single biochemical markers and those deriving from the most recent studies of metabolomics.

A retrospective study on IVF outcome in euthyroid patients with anti-thyroid antibodies: effects of levothyroxine, acetyl-salicylic acid and prednisolone adjuvant treatments.

BACKGROUND: Anti-thyroid antibodies (ATA), even if not associated with thyroid dysfunction, are suspected to cause poorer outcome of in vitro fertilization (IVF). METHODS: We retrospectively analyzed: (a) the prevalence of ATA in euthyroid infertile women, (b) IVF outcome in euthyroid, ATA+ patients, and (c) the effect of adjuvant treatments (levothyroxine alone or associated with acetylsalicylic acid and prednisolone) on IVF results in ATA+ patients. One hundred twenty-nine euthyroid, ATA+ women undergoing IVF were compared with 200 matched, ATA-controls. During IVF cycle, 38 ATA+ patients did not take any adjuvant treatment, 55 received levothyroxin (LT), and 38 received LT +acetylsalicylic acid (ASA)+prednisolone (P). RESULTS: The prevalence of ATA among euthyroid, infertile patients was 10.5%, similar to the one reported in euthyroid women between 18 and 45 years. ATA+ patients who did not receive any adjuvant treatment showed significantly poorer ovarian responsiveness to stimulation and IVF results than controls. ATA+ patients receiving LT responded better to ovarian stimulation, but had IVF results as poor as untreated ATA+ women. Patients receiving LT+ASA+P had significantly higher pregnancy and implantation rates than untreated ATA+ patients (PR/ET 25.6% and IR 17.7% vs. PR/ET 7.5% and IR 4.7%, respectively), and overall IVF results comparable to patients without ATA (PR/ET 32.8% and IR 19%). CONCLUSION: These observations suggest that euthyroid ATA+ patients undergoing IVF could have better outcome if given LT+ASA+P as adjuvant treatment. This hypothesis must be verified in further randomized, prospective studies.

Cardiovascular Risk Factors in Children and Adolescents With Obesity: Sex-Related Differences and Effect of Puberty.

Objectives: To evaluate the effect of gender and puberty on cardiovascular risk factors (CVRF) in obese children and adolescents. Methods: One thousand four hundred and nine obese patients [age 9.7 (2.2-17.9) y; 646 Male] were studied. Subjects were stratified according to Tanner pubertal staging and age into prepubertal ≤ and >6 ys (G1 and G2), pubertal stage 2-3 (G3), and pubertal stage 4-5 (G4). Waist circumference (WC), systolic and diastolic blood pressure (SP, DP), fasting plasma glucose, insulin, post Oral Glucose Tolerance Test glucose and insulin, and lipids were evaluated. Insulin resistance was evaluated by HOMA index. Patients with no CVRF were considered metabolically healthy (MHO). Results: The percentage of MHO patients was 59.8% in G1 while was consistently around 30% in the other groups. WC was more frequently abnormal in G2 males. Pubertal progression was associated with a decrease in WC abnormalities. SP was more frequently abnormal in G4 males and pubertal progression was associated with higher prevalence of abnormal SP in males. Pubertal progression was associated with an increase in hypertension rate in both sexes. HOMA was more frequently abnormal in G2 and G3 females. HDL, LDL, and TG were more frequently abnormal in G2 females. Dyslipidemia rate was higher in G2 females. Pubertal progression was associated with higher prevalence of abnormal HDL in males. Conclusions: Sex and pubertal status influence the frequency of abnormalities of CVRF in obese children and adolescents. CVRF are already present in prepubertal age. Identifying patients with higher risk of metabolic complications is important to design targeted and effective prevention strategies.

Fertility preservation in BRCA mutation carriers.

Interest in fertility preservation for young women facing gonadotoxic therapies is increasing according to enhanced long-term survival rates of these patients. Women who carry a mutation in the BRCA1 or BRCA2 gene have a specifically increased lifetime risk of developing breast and tubo-ovarian cancer. Moreover, they are at high risk of undergoing premature infertility due to the medical interventions that are often performed in order to reduce cancer risk or treat an already existing malignancy. Fertility issues are relevant for healthy BRCA mutation carriers, whose family-planning decisions are often influenced by the need of prophylactic bilateral salpingo-oophorectomy at young age. In BRCA mutation carriers who have a breast cancer at young age, the oncostatic treatment is associated with a significant ovarian toxicity linked to chemotherapy as well as to the long lasting hormonotherapy and to the need of delaying pregnancy for several years. Prompt counselling about different fertility preservation options should be offered to all young girls and women at high risk of ovarian insufficiency and infertility. Validated techniques to preserve fertility include oocyte and embryo cryopreservation, while experimental techniques include ovarian suppression with GnRH-analogues during chemotherapy and ovarian tissue cryopreservation. The choice of the best strategy depends on age, type of chemotherapy, partner status, cancer type, time available for fertility preservation intervention and the risk of ovarian metastasis. All available options should be offered and can be performed alone or in combination. A crucial point is to avoid a significant delay to cancer treatment.

Fertility preservation in BRCA mutation carriers.

According to enhanced long-term survival rates of these patients, interest in fertility preservation for young women facing gonadotoxic therapies is increasing. Women who carry a mutation in the BRCA1 or BRCA2 gene have a specifically increased lifetime risk of developing breast and tubo-ovarian cancer. Moreover, they are at high risk of undergoing premature infertility due to the medical interventions that are often performed in order to reduce cancer risk or treat an already existing malignancy. Fertility issues are relevant for healthy BRCA mutation carriers, whose family-planning decisions are often influenced by the need of prophylactic bilateral salpingo-oophorectomy at young age. In BRCA mutation carriers who have a breast cancer at young age, the oncostatic treatment is associated with a significant ovarian toxicity linked to chemotherapy as well as to the long lasting hormonotherapy and to the need of delaying pregnancy for several years. Prompt counselling about different fertility preservation options should be offered to all young girls and women at high risk of ovarian insufficiency and infertility. Validated techniques to preserve fertility include oocyte and embryo cryopreservation, while experimental techniques include ovarian suppression with GnRH-analogs during chemotherapy and ovarian tissue cryopreservation. The choice of the best strategy depends on age, type of chemotherapy, partner status, cancer type, time available for fertility preservation intervention and the risk of ovarian metastasis. All available options should be offered and can be performed alone or in combination. A crucial point is to avoid a significant delay to cancer treatment.