Vitamin and mineral needs during the oral contraceptive therapy: a systematic review

Objectives: There is growing evidence that women using OCs change in serum trace elements and vitamins. Nowadays, in many cases, side effects associated with low levels of micronutrients are not considered during oral contraceptives (OCs) therapy. This review aims at checking the present literature in order to verify the evidences. Our purpose is to underline this aspect contributing to improve the therapeutic approach with OCs.Methods: Systematic literature search was performed in electronic databases, covering the period from January 1967 to January 2012.Results: Ninety-five articles were located; a cross sectional randomized and three RCTs studies were considered eligible.Conclusions: A decrease in the serum concentrations of zinc, selenium, phosphorus and magnesium have been reported in OC users. Such reductions were proportional to the duration of contraceptive use. These reductions may imply a reduction in the probability of having a pregnancy and/or an increase of serious illness for the unborn. In this regard, a supplementation with the above compounds could be useful in OC users, namely for reducing side effects

Impact of Maternal Age on Oocyte and Embryo Competence

The overall success of human reproduction, either spontaneously or after IVF, is highly dependent upon maternal age. The main reasons for age-related infertility include reduced ovarian reserve and decreased oocyte/embryo competence due to aging insults, especially concerning an increased incidence of aneuploidies and possibly decreased mitochondrial activity. Age-related chromosomal abnormalities mainly arise because of meiotic impairments during oogenesis, following flawed chromosome segregation patterns such as non-disjunction, premature separation of sister chromatids, or the recent reverse segregation. In this review, we briefly discuss the main mechanisms putatively impaired by aging in the oocytes and the deriving embryos. We also report the main strategies proposed to improve the management of advanced maternal age women in IVF: fertility preservation through oocyte cryopreservation to prevent aging; optimization of the ovarian stimulation and enhancement of embryo selection to limit its effects; and oocyte donation to circumvent its consequences

Follicular versus luteal phase ovarian stimulation during the same menstrual cycle (DuoStim) in a reduced ovarian reserve population results in a similar euploid blastocyst formation rate: new insight in ovarian reserve exploitation

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DuoStim – a reproducible strategy to obtain more oocytes and competent embryos in a short time-frame aimed at fertility preservation and IVF purposes. A systematic review

Recent evidence suggests that follicular development occurs in a wave-like model during the ovarian cycle, where up to three cohorts of follicles are recruited to complete folliculogenesis. This understanding overtakes the previous dogma stating that follicles grow only during the follicular phase of the menstrual cycle. Therefore, in in vitro fertilization (IVF), novel protocols regarding ovarian stimulation have been theorized based on the use of gonadotrophins to prompt the growth of antral follicles at any stage of the menstrual cycle. These unconventional protocols for ovarian stimulation aim at a more efficient management of poor-prognosis patients, otherwise exposed to conflicting outcomes after conventional approaches. DuoStim appears among these unconventional stimulation protocols as one of the most promising. It combines two consecutive stimulations in the follicular and luteal phases of the same ovarian cycle, aimed at increasing the number of oocytes retrieved and embryos produced in the short time-frame. This protocol has been suggested for the treatment of all conditions requiring a maximal and urgent exploitation of the ovarian reserve, such as oncological patients and poor responders at an advanced maternal age. At present, data from independent studies have outlined the consistency and reproducibility of this approach, which might also reduce the drop-out between consecutive failed IVF cycles in poor-prognosis patients. However, the protocol must be standardized, and more robust studies and cost-benefit analyses are needed to highlight the true clinical pros and cons deriving from DuoStim implementation in IVF

Severe male factor in in vitro fertilization: definition, prevalence, and treatment. An update

Infertility affects 10%-15% of couples worldwide. Of all infertility cases, 20%-70% are due to male factors. In the past, men with severe male factor (SMF) were considered sterile. Nevertheless, the development of intracytoplasmic sperm injection (ICSI) drastically modified this scenario. The advances in assisted reproductive technology (ART), specifically regarding surgical sperm retrieval procedures, allowed the efficacious treatment of these conditions. Yet, before undergoing ICSI, male factor infertility requires careful evaluation of clinical and lifestyle behavior together with medical treatment. Epidemiologically speaking, women whose male partner is azoospermic tend to be younger and with a better ovarian reserve. These couples, in fact, are proposed ART earlier in their life, and for this reason, their ovarian response after stimulation is generally good. Furthermore, in younger couples, azoospermia can be partially compensated by the efficient ovarian response, resulting in an acceptable fertility rate following in vitro fertilization (IVF) techniques. Conversely, when azoospermia is associated with a reduced ovarian reserve and/or advanced maternal age, the treatment becomes more challenging, with a consequent reduction in IVF outcomes. Nonetheless, azoospermia seems to impair neither the euploidy rate at the blastocyst stage nor the implantation of euploid blastocysts. Based on the current knowledge, the assessment of male infertility factors should involve: (1) evaluation - to diagnose and quantify seminologic alterations; (2) potentiality - to determine the real possibilities to improve sperm parameters and/or retrieve spermatozoa; (3) time - to consider the available "treatment window", based on maternal age and ovarian reserve. This review represents an update of the definition, prevalence, causes, and treatment of SMF in a modern ART clinic

Reduction of multiple pregnancies in the advanced maternal age population after implementation of an elective single embryo transfer policy coupled with enhanced embryo selection: Pre- and post-intervention study

STUDY QUESTION Is an elective single-embryo transfer (eSET) policy an efficient approach for women aged >35 years when embryo selection is enhanced via blastocyst culture and preimplantation genetic screening (PGS)? SUMMARY ANSWER Elective SET coupled with enhanced embryo selection using PGS in women older than 35 years reduced the multiple pregnancy rates while maintaining the cumulative success rate of the IVF programme. WHAT IS KNOWN ALREADY Multiple pregnancies mean an increased risk of premature birth and perinatal death and occur mainly in older patients when multiple embryos are transferred to increase the chance of pregnancy. A SET policy is usually recommended in cases of good prognosis patients, but no general consensus has been reached for SET application in the advanced maternal age (AMA) population, defined as women older than 35 years. Our objective was to evaluate the results in terms of efficacy, efficiency and safety of an eSET policy coupled with increased application of blastocyst culture and PGS for this population of patients in our IVF programme. STUDY DESIGN, SIZE, DURATION In January 2013, a multidisciplinary intervention involving optimization of embryo selection procedure and introduction of an eSET policy in an AMA population of women was implemented. This is a retrospective 4-year (January 2010-December 2013) pre- and post-intervention analysis, including 1161 and 499 patients in the pre- and post-intervention period, respectively. The primary outcome measures were the cumulative delivery rate (DR) per oocyte retrieval cycle and multiple DR. PARTICIPANTS/MATERIALS, SETTING, METHODS Surplus oocytes and/or embryos were vitrified during the entire study period. In the post-intervention period, all couples with good quality embryos and less than two previous implantation failures were offered eSET. Embryo selection was enhanced by blastocyst culture and PGS (blastocyst stage biopsy and 24-chromosomal screening). Elective SET was also applied in cryopreservation cycles. MAIN RESULTS AND THE ROLE OF CHANCE Patient and cycle characteristics were similar in the pre- and post-intervention groups [mean (SD) female age: 39.6 ± 2.1 and 39.4 ± 2.2 years; range 36-44] as assessed by logistic regression. A total of 1609 versus 574 oocyte retrievals, 937 versus 350 embryo warming and 138 versus 27 oocyte warming cycles were performed in the pre- and post-intervention periods, respectively, resulting in 1854 and 508 embryo transfers, respectively. In the post-intervention period, 289 cycles were blastocyst stage with (n = 182) or without PGS (n = 107). A mean (SD) number of 2.9 ± 1.1 (range 1-4) and 1.4 ± 0.8 (range 1-3) embryos were transferred pre- and post-intervention, respectively (P < 0.01) and similar cumulative clinical pregnancy rates per transfer and per cycle were obtained: 26.8, 30.9% and 29.7, 26.3%, respectively. The total DR per oocyte retrieval cycle (21.0 and 20.4% pre- and post-intervention, respectively) defined as efficacy was not affected by the intervention [odds ratio (OR) = 0.8, 95% confidence interval (CI) = 0.7-1.1; P = 0.23]. However, a significantly increased live birth rate per transferred embryo (defined as efficiency) was observed in the post-intervention group 17.0 versus 10.6% (P < 0.01). Multiple DRs decreased from 21.0 in the preintervention to 6.8% in the post-intervention group (OR = 0.3. 95% CI = 0.1-0.7; P < 0.01). LIMITATIONS, REASONS FOR CAUTION In this study, the suitability of SET was assessed in individual women on the basis of both clinical and embryological prognostic factors and was not standardized. For the described eSET strategy coupled with an enhanced embryo selection policy, an optimized culture system, cryopreservation and aneuploidy screening programme is necessary. WIDER IMPLICATIONS OF THE FINDINGS Owing to the increased maternal morbidity and perinatal complications related to multiple pregnancies, it is recommended to extend the eSET policy to the AMA population. As shown in this study, enhanced embryo selection procedures might allow a reduction in the number of embryos transferred and the number of transfers to be performed without affecting the total efficacy of the treatment but increasing efficiency and safety. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology

Advanced Maternal Age in IVF: Still a Challenge? The Present and the Future of Its Treatment

Advanced maternal age (AMA; >35 year) is associated with a decline in both ovarian reserve and oocyte competence. At present, no remedies are available to counteract the aging-related fertility decay, however different therapeutic approaches can be offered to women older than 35 year undergoing IVF. This review summarizes the main current strategies proposed for the treatment of AMA: (i) oocyte cryopreservation to conduct fertility preservation for medical reasons or “social freezing” for non-medical reasons, (ii) personalized controlled ovarian stimulation to maximize the exploitation of the ovarian reserve in each patient, (iii) enhancement of embryo selection via blastocyst-stage preimplantation genetic testing for aneuploidies and frozen single embryo transfer, or (iv) oocyte donation in case of minimal/null residual chance of pregnancy. Future strategies and tools are in the pipeline that might minimize the risks of AMA through non-invasive approaches for embryo selection (e.g., molecular analyses of leftover products of IVF, such as spent culture media). These are yet challenging but potentially ground-breaking perspectives promising a lower clinical workload with a higher cost-effectiveness. We also reviewed emerging experimental therapeutic approaches to attempt at restoring maternal reproductive potential, e.g., spindle-chromosomal complex, pronuclear or mitochondrial transfer, and chromosome therapy. In vitro generation of gametes is also an intriguing challenge for the future. Lastly, since infertility is a social issue, social campaigns, and education among future generations are desirable to promote the awareness of the impact of age and lifestyle habits upon fertility. This should be a duty of the clinical operators in this field

Management of Poor Responders in IVF: Is There Anything New?

Despite the fact that in the last two decades an enormous number of papers on the topic of poor ovarian response have been published in the literature, so far it has been impossible to identify any efficient treatment to improve the ovarian response and the clinical outcome of this group of patients. The incidence of poor ovarian responders among infertile women has been estimated at 9–24% but according to recent reviews, it seems to have slightly increased. The limitation in quantifying the incidence of these patients among the infertile population is due to the difficulty of a clear definition in literature. A recent paper by the Bologna ESHRE working group on poor ovarian response has been the first real attempt to find a common definition. Current literature proposes new risk factors which could be the cause of a reduction in ovarian reserve, which also includes genetic factors. This represents the first necessary step towards finding applicable solutions for these patients. To date, there is a substantial lack of literature that identifies an ideal protocol for these patients. The use of the “Bologna criteria” and the introduction of long acting gonadotropin in clinical practice have given rise to new promising stimulation protocols for this group of patients

Management of Poor Responders in IVF: Is There Anything New?

Despite the fact that in the last two decades an enormous number of papers on the topic of poor ovarian response have been published in the literature, so far it has been impossible to identify any efficient treatment to improve the ovarian response and the clinical outcome of this group of patients. The incidence of poor ovarian responders among infertile women has been estimated at 9-24% but according to recent reviews, it seems to have slightly increased. The limitation in quantifying the incidence of these patients among the infertile population is due to the difficulty of a clear definition in literature. A recent paper by the Bologna ESHRE working group on poor ovarian response has been the first real attempt to find a common definition. Current literature proposes new risk factors which could be the cause of a reduction in ovarian reserve, which also includes genetic factors. This represents the first necessary step towards finding applicable solutions for these patients. To date, there is a substantial lack of literature that identifies an ideal protocol for these patients. The use of the "Bologna criteria" and the introduction of long acting gonadotropin in clinical practice have given rise to new promising stimulation protocols for this group of patients

Effect of Myoinositol and Antioxidants on Sperm Quality in Men with Metabolic Syndrome

This prospective longitudinal study investigated the effects of a dietary supplement in patients affected by reduced sperm motility (asthenospermic males) with metabolic syndrome. The product tested was Andrositol®, which contains myoinositol (MI) as principal compound, in association with other molecules, and the parameters evaluated were semen characteristics as well as hormone and metabolic profiles. The inclusion criteria were subjects aged over 18 years, with asthenospermia and metabolic syndrome. The exclusion criteria were presence of cryptorchidism, varicocele, and prostatitis. For this study, 45 males who had such features were enrolled. Their selection was made according to the 2010 World Health Organization (WHO) criteria (5th Edition) for the Evaluation of Human Semen. Hormone and metabolic profiles and semen parameters were assessed at the beginning of the study and after three months of treatment with Andrositol. The differences between the values before and after the supplementation were found statistically significant. Andrositol normalized the metabolic profile of these patients, improving their insulin sensitivity. Moreover, testosterone levels were increased and the semen characteristics, such as sperm concentration, motility, and morphology, highly improved. In conclusion, the association of MI with other molecules (micronutrients and vitamins) could be an effective therapy for metabolic disorders, as well as hormonal and spermatic changes responsible for male infertility