In the last years, thanks to the improvement in the prognosis of cancer patients, a growing attention has been given to the fertility issues. International guidelines on fertility preservation in cancer patients recommend that physicians discuss, as early as possible, with all patients of reproductive age their risk of infertility from the disease and/or treatment and their interest in having children after cancer, and help with informed fertility preservation decisions. As recommended by the American Society of Clinical Oncology and the European Society for Medical Oncology, sperm cryopreservation and embryo/oocyte cryopreservation are standard strategies for fertility preservations in male and female patients, respectively; other strategies (e.g. pharmacological protection of the gonads and gonadal tissue cryopreservation) are considered experimental techniques. However, since then, new data have become available, and several issues in this field are still controversial and should be addressed by both patients and their treating physicians. In April 2015, physicians with expertise in the field of fertility preservation in cancer patients from several European countries were invited in Genova (Italy) to participate in a workshop on the topic of “cancer and fertility preservation”. A total of ten controversial issues were discussed at the conference. Experts were asked to present an up-to-date review of the literature published on these topics and the presentation of own unpublished data was encouraged. On the basis of the data presented, as well as the expertise of the invited speakers, a total of ten recommendations were discussed and prepared with the aim to help physicians in counseling their young patients interested in fertility preservation. Although there is a great interest in this field, due to the lack of large prospective cohort studies and randomized trials on these topics, the level of evidence is not higher than 3 for most of the recommendations highlighting the need of further research efforts in many areas of this field. The participation to the ongoing registries and prospective studies is crucial to acquire more robust information in order to provide evidence-based recommendations.

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Cancer and fertility preservation: international recommendations from an expert meeting

Background Gonadotropin-releasing hormone (GnRH) antagonist protocols for pituitary down regulation in in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) allow the use of GnRH agonists for triggering final oocyte maturation. Currently, human chorionic gonadotropin (HCG) is still the standard medication for this purpose. The effectiveness of triggering with a GnRH agonist compared to HCG measured as pregnancy and ovarian hyperstimulation(OHSS) rates are unknown. Objectives To compare the effectiveness of a GnRH agonist with HCG for triggering final oocyte maturation in IVF and ICSI patients undergoing controlled ovarian hyperstimulation in a GnRH antagonist protocol followed by embryo transfer. Search strategy We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE , EMBASE, the National Research Register, the Medical Research Council's Clinical Trials Register, and the NHS Centre for Reviews and Dissemination database. We also examined the reference lists of all known primary studies and review articles, citation lists of relevant publications and abstracts of major scientific meetings. Selection criteria All randomised controlled studies (RCTs) reporting data comparing clinical outcomes for women undergoing IVF and ICSI cycles and using a GnRH agonist in comparison with HCG for final oocyte maturation triggering. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Main results We identified 11 RCTs (n = 1055). Eight studies assessed fresh autologous cycles and three studies assessed donor-recipient cycles. In fresh-autologous cycles, GnRH agonist was less effective than HCG in terms of the live birth rate per randomised woman (OR 0.44, 95% CI 0.29 to 0.68; 4 RCTs) and ongoing pregnancy rate per randomised woman (OR 0.45, 95% CI 0.31 to 0.65; 8 RCTs). For a group with a 30% live birth or ongoing pregnancy rate using HCG, the rate would be between 12% and 22% using an GnRH agonist. Moderate to severe ovarian hyperstimulation syndrome (OHSS) incidence per randomised woman was significantly lower in the GnRH agonist group compared to the HCG group (OR 0.10, 95% CI 0.01 to 0.82; 5 RCTs). For a group with a 3% OHSS rate using HCG the rate would be between 0% and 2.6% using GnRH agonist. In donor recipient cycles, there was no evidence of a statistical difference in the live birth rate per randomised woman (OR 0.92, 95% CI 0.53 to 1.61; 1 RCT). Authors' conclusions We do not recommend that GnRH agonists be routinely used as a final oocyte maturation trigger in fresh autologous cycles because of lowered live birth rates and ongoing pregnancy rates. An exception could be made for women with high risk of OHSS, after appropriate counselling.

Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology

Human male infertility is often related to chromosome abnormalities. In chromosomally normal infertile males, the rates of chromosome 21 and sex chromosome disomy in spermatozoa are increased. Higher incidences of trisomy 21 (seldom of paternal origin) and sex chromosome aneuploidy are also found. XXY and XYY patients produce increased numbers of XY, XX and YY spermatozoa, indicating an increased risk of production of XXY, XYY and XXX individuals. Since XXYs can reproduce using intracytoplasmic sperm injection (ICSI), this could explain the slight increase of sex chromosome anomalies in ICSI series. Carriers of structural reorganizations produce unbalanced spermatozoa, and risk having children with duplications and/or deficiencies. In some cases, this risk is considerably lower or higher than average. These patients also show increased diploidy, and a higher risk of producing diandric triploids. Meiotic disorders are frequent in infertile males, and increase with severe oligoasthenozoospemia (OA) and/or high follicle stimulating hormone (FSH) concentrations. These patients produce spermatozoa with autosomal and sex chromosome disomies, and diploid spermatozoa. Their contribution to recurrent abortion depends on the production of trisomies, monosomies and of triploids. The most frequent sperm chromosome anomaly in infertile males is diploidy, originated by either meiotic mutations or by a compromised testicular environment.

Human male infertility: chromosome anomalies, meiotic disorders, abnormal spermatozoa and recurrent abortion

Reproductive difficulties are associated intimately with cytogenetic abnormalities. This article reviews multicolour fluorescence in situ hybridization studies on spermatozoa from men with constitutional chromosomal abnormalities and the consequences for spermatozoa, and on chromosomal abnormalities in the spermatozoa of infertile men who have normal somatic karyotypes. In 47,XYY men, the frequencies of 24,XY and 24,YY spermatozoa appear to be < or = 1%. Klinefelter (47,XXY) and mosaic Klinefelter patients had sperm aneuploidy frequencies of 2-25% and 1.5-7.0%, respectively. Robertsonian translocation carriers had 3-27% spermatozoa unbalanced for the chromosomes involved in the translocation, with a possible modest interchromosomal effect, but none of the increased frequencies of chromosomal disomy approached 1%. The frequency of chromosomally unbalanced spermatozoa in reciprocal translocations averages 50%, is strongly dependent on the chromosomes involved in the individual translocation, and may be slightly increased as a result of a small interchromosomal effect. Infertile men with a normal karyotype and low sperm concentration or certain types of morphologically abnormal spermatozoa have a significantly increased risk of producing aneuploid spermatozoa, particularly for the sex chromosomes. An increased risk of sperm aneuploidy was not observed in infertile men with poor sperm motility or in those with a normal karyotype and normal semen parameters.

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Aneuploidy in human spermatozoa : FISH analysis in men with constitutional chromosomal abnormalities, and in infertile men

Application of fluorescence in situ hybridization (FISH) analysis has opened the way for comprehensive studies on numerical chromosome abnormalities in human sperm. During the last decade, more than five million sperm from approximately 500 normal men were analyzed by a number of laboratories from around the world by this approach. Except for chromosome 19 which has been analyzed in only one study, all other chromosomes have been examined by two or more studies with considerable differences in disomy frequency for an individual chromosome among studies. The mean disomy frequency is 0.15% for each of the autosomes and 0.26% for the sex chromosomes. Most chromosomes analyzed have an equal distribution of disomy with the exception of chromosomes 14, 21, 22 and the sex chromosomes, which display significantly higher disomy frequencies. Slight but significant increases in disomy frequency with advancing paternal age were observed for some chromosomes, in particular for the sex chromosomes. Some lifestyle factors such as smoking, alcohol drinking and caffeine consumption have been investigated and no consistent association between disomy frequency and any type of lifestyle factors has been established. The question of whether different geographic and ethnic groups of men have inherent differences in frequency of disomic sperm has been investigated by two studies with conflicting results.

Aneuploidy in human sperm: a review of the frequency and distribution of aneuploidy, effects of donor age and lifestyle factors.

Chromosome translocations have been known to affect disjunction of chromosomes unrelated to the translocation in the mouse and in Drosophila. However, in humans, an interchromosomal effect in chromosome translocations has not been demonstrated. The availability of techniques that allow the study of nondisjunction in sperm cells has permitted us to evaluate the possibility of an interchromosomal effect in male translocation heterozygotes. In this study, multicolor fluorescence in situ hybridization was used to determine levels of disomy for the clinically relevant chromosomes X, Y, 13, 18, and 21 in 332,858 spermatozoa from nine reciprocal translocation heterozygotes and nine controls with normal karyotypes. The specific translocations studied were as follows: t(10;12)(p26.1;p13.3), t(2;18)(p21;q11.2), t(3;19)(p25;q12), t(5;8)(q33;q13), t(11;22)(q23;q11), t(3;4)(p25;p16), t(8;9)(q24.2;q32), t(10;18)(q24.1;p11.2), and t(4;10)(q33;p12.2). Comparisons of disomy rates between carriers and controls were performed by using the Mann-Whitney test. Our results showed that the rates of sex chromosome hyperhaploidy were similar in controls (0.21%) and in translocation carriers (0.19%). Similarly, the frequencies of disomy for chromosomes 13, 18, and 21 did not differ significantly between controls and carriers (0.05% versus 0.08%, 0.07% versus 0.03%, and 0.14% versus 0.20%, respectively). Sex chromosome nondisjunction was more common than nondisjunction of chromosomes 13 and 18 both in controls (P=0.0057) and in carriers (P=0.0008). Similarly, the rates of chromosome disomy for chromosome 21 were higher than those for chromosomes 13 and 18 in both controls (P=0.0031) and translocation carriers (P=0.0057). In our study, the excess of chromosome 21 disomy versus disomy of the other autosomes was more pronounced in carriers than in controls. Thus, although the difference of disomy 21 between controls and carriers was not statistically significant, it is worthy of attention.

Is there an interchromosomal effect in reciprocal translocation carriers? Sperm FISH studies.

Random-start gonadotropin-releasing hormone (GnRH) antagonist-treated cycles with GnRH agonist trigger for fertility preservation.

The relationship between perceived stress, acupuncture, and pregnancy rates among IVF patients: A pilot study

https://www.fertstert.org/article/S0015-0282(08)04681-5/pdf

Gonadotropin-releasing hormone agonist or human chorionic gonadotropin for final oocyte maturation in an oocyte donor program.

. The sperm products of two male carriers of reciprocal translocations were studied by fluorescence in situ hybridization (FISH) using a combination of three probes for each trans

Anthony N. Wakim

Papers

Is there an interchromosomal effect in reciprocal translocation carriers? Sperm FISH studies.

Random-start gonadotropin-releasing hormone (GnRH) antagonist-treated cycles with GnRH agonist trigger for fertility preservation.

The relationship between perceived stress, acupuncture, and pregnancy rates among IVF patients: A pilot study

Gonadotropin-releasing hormone agonist or human chorionic gonadotropin for final oocyte maturation in an oocyte donor program.

Meiotic products of two reciprocal translocations studied by multicolor fluorescence in situ hybridization.