Varicocelectomy – The Unkindest Cut of All

Round spermatid nucleus injection (ROSNI)

Recent loss of rhinoceros subspecies has renewed interest in using more advanced assisted reproductive technologies (ART) in rhinoceroses and elephants. Currently, only semen collection, semen preservation and artificial insemination (AI) have been used repeatedly with success in these species. Although ovum pick-up (OPU) and intra-cytoplasmic sperm injection (ICSI) have been reported recently in rhinoceroses, the techniques are not yet optimised. In contrast, multiple ART applications are routinely used in the horse. Since elephants and rhinoceroses share some reproductive features with equids, we postulate that procedures such as OPU, ICSI, in vitro fertilisation (IVF) and embryo transfer (ET), which are well established in the horse, may represent a basis to develop protocols for endangered pachyderms. In this review, we summarise current knowledge on reproductive physiology relevant to ART. We discuss the current state of ART in all three families and the requirements for the successful implementation of OPU, ICSI, IVF and ET in these species.Lay summaryWild rhinoceros and elephant populations are facing ongoing threats; therefore, additional measures are required to protect these species for future generations. Assisted reproductive technologies (ART) include the collection of semen to directly inseminate females or to fertilise oocytes (eggs) in a laboratory to produce embryos, which can be transferred into a recipient female at a later date. While these techniques are routinely used in humans and domestic animals such as the horse, more research is needed to incorporate such technologies into the breeding of elephants and rhinoceroses. As the horse is the closest related domestic species to the rhinoceros, it may serve as the best possible role model. We discuss the current state of ART in the horse, elephant and rhinoceros and the possibilities for future use of these techniques in breeding such endangered animals.

The slippery slopes of advanced reproductive technologies: Presidential address

Many wild equids are at present endangered in the wild. Concurrently, increased mechanization has pushed back the numbers of some old native horse breeds to levels that are no longer compatible with survival of the breed. Strong concerns arose in the last decade to preserve animal biodiversity, including that of rare horse breeds. Genome Resource Banking refers to the cryostorage of genetic material and is an approach for ex situ conservation, which should be applied in combination with in situ conservation programmes. In this review, we propose that, owing to the great reproductive similarity among the different members of the genus Equus, the domestic horse can be used to optimize cryopreservation and embryo production protocols for future application in wild equids. We will give this hypothesis a scientific underpinning by listing successful applications of epididymal sperm freezing, embryo freezing, intracytoplasmic sperm injection, oocyte vitrification and somatic cell nuclear transfer in domestic horses. Some ART fertilization methods may be performed with semen of very low quality or with oocytes obtained after the death of the mare.

Advanced assisted reproductive technologies such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are established treatment for severe male-factor infertility. The risk of transmitting existing genetic abnormalities to offspring through assisted reproduction has been a particular concern in male infertility cases due to Y-chromosome microdeletion, congenital bilateral absence of the vas deferens and Klinefelter’s syndrome, because these conditions generally required ICSI to achieve pregnancy. In addition, earlier studies raised the concerns of increased spontaneous abortion rate and chromosomal abnormalities with IVF and ICSI. Recently, well designed, large scale, population based studies concluded that assisted reproductive technology accounts for a more than a two-fold increase in the risk of low birth weight and major birth defects. Taken together, the bulk of the literature on the genetic risks of assisted reproduction highlights the importance of adequate pretreatment genetic evaluation and counselling. Furthermore, it is important to have proper infertility evaluation to identify and treat reversible causes of male-factor infertility that would allow couples to conceive naturally or opt for less invasive assisted reproductive technology.

Of all sexually active couples, 12–15% are infertile. When broken down by gender, a male component can be identified 50% of the time either in isolation or in combination with a female factor. The majority of the causes of male infertility are treatable or preventable, so a keen understanding of these conditions is paramount. Despite advancements in assisted reproductive technologies, the goal of a male infertility specialist is not simply to retrieve sperm. Instead, the male infertility specialist attempts to optimize a male’s reproductive potential and thereby allow a couple to conceive successfully through utilization of less invasive reproductive techniques. Often, this involves the use of sperm or testicular tissue cryopreservation prior to fertility insult. At the same time, the male fertility specialist is wary of underlying or causal, potentially serious medical or genetic conditions that prompted reproductive evaluation. Previous research in a US male fertility clinic analyzing 1,430 patients identified causes of infertility from most to least common: varicocele, idiopathic, obstruction, female factor, cryptorchidism, immunologic, ejaculatory dysfunction, testicular failure, drug effects/radiation, endocrinology, and all others. The focus of this book on the role of reactive oxygen species (ROS) is easily applied to the majority of the listed conditions (described in detail in later chapters) which comprise this chapter’s overview of pre-testicular, testicular, and post-testicular causes of male infertility.

The slippery slopes of advanced reproductive technologiesPresidential address

After completing this article, readers should be able to: 1. Describe the outcomes of assisted reproductive technologies (ART) for singleton, twin, and other multiple births. 2. Describe the role of fertility in adverse outcomes seen with ART births. 3. Review the association of birth defects with ART. 4. Delineate the association of disease of genomic imprinting with ART. 5. Describe the relationship between ART and the subsequent incidence of neurodevelopmental sequelae. In the 1977 ruling “Carey v. Population Services International,” the United States Supreme Court ruled that the decision to bear children is constitutionally protected. (1) Significant interest already had been shown in the development and improvements of in vitro fertilization (IVF) for infertile couples. The first human pregnancy and human birth using IVF were reported by Steptoe and Edwards in the United Kingdom. (2) Their work resulted in the first baby born via reproductive technologies, Louise Brown, born on July 25, 1978, at Oldham General Hospital in Oldham, United Kingdom. (3) She was born via a planned cesarean section, and her birthweight was 2.61 kg. The first successful viable IVF in the United States was performed by Jones and Seager-Jones in 1981 in Norfolk, Virginia. (4) Assisted reproductive technologies (ART) have seen a recent surge in popularity. The Centers for Disease Control and Prevention (CDC) reported that 122,872 cycles of ART were initiated in 2003, resulting in the delivery of 48,756 neonates, (5) accounting for approximately 1% of all neonates delivered in the United States. The percentage is higher in many countries, including Denmark, where it is estimated that 5% of all deliveries are with the assistance of ART. (6) Couples pursue ART for myriad reasons, including tubal transport factors, ovulatory dysfunction, uterine factors, endometriosis, male- and female-specific factors, and when a cause of infertility is unknown. (5) It would be very …

With gender equality and the ‘modern family’, the pace for advances in artificial reproductive technology is fast-moving. Louise Brown was the world's first ‘test tube baby’, born in 1978 (Steptoe & Edwards. Lancet 1978;2:366) (Figure 1). However, infertility and reproductive medicine have featured heavily in ancient mythology of many cultures, reflecting their long-standing value in human society. The Hippocratic Corpus from the 5th and 4th centuries BCE include three chapters on gynaecology and infertility, where infertility had become a medicalised concept and treatment options were proposed. Coxe's translation lists five causes of infertility: ‘the os uteri wrongly situated and firmly closed; the lubricity of the uterus preventing the retention of the seed; ulceration of the body of the uterus consequent to other diseases; retention of the menses; and too great laxity of the orifice of the uterus, precluding the retention of the seed’. Remedies for these afflictions included instrumentation of the stenosed cervical os, a multitude of pessaries containing herbal remedies, fumigation techniques, and specific instructions regarding the timing and method of intercourse (Coxe. The Writings of Hippocrates and Galen, Lindsay & Blakiston, Philadelphia, 306–7). There is also mention of ‘somatic’ or systemic causes, including what we now know as obesity (Flemming. Bull Hist Med 2013;87:565–90). The medicalisation of infertility improved understanding of anatomy and the advent of microscopy drove significant advancements during the 17th century. In 1672, Regnier de Graaf described the ovarian follicles now named after him, at the time believed to be the embryo that migrated to the uterus (Ankum et al. Hum Reprod Update 1996;2:365–9). Spermatozoa was first described in 1677 by microbiologist Anthoni van Leeuwenhoek, who hesitantly inspected his own semen. He wrote to the Royal Society of London stating, ‘If your Lordship should consider that these observations may disgust or scandalise the learned, I earnestly beg your Lordship to regard them as private and to publish or destroy them, as your Lordship sees fit’ (Philos Trans R Soc 1678;12:1040–3). William Smellie wrote on the concept of fertilisation in 1752, outlining the process of ovulation, transit of the ovum through the fallopian tube, and describing semen as ‘abounding with animalcula, that swim about in it like so many tadpoles’ (Smellie. A treatise on the theory and practice of midwifery, Balliere Tindall, London, 1974 reprint; 113–4). Spallanzani pioneered artificial insemination in 1784, achieving pregnancy in dogs, while Dr John Hunter performed the first successful artificial insemination in a human in 1790 for a man with hypospadias (Guttmacher. Ann NY Acad Sci 1962;97:623–31). Contrast this gradual development in reproductive medicine since Hippocrates with the 40 years since Louise Brown's birthday in 1978. The advances in reproductive technology – sperm and egg donors, intracytoplasmic sperm injection, frozen intravenous fertilisation cycles, surrogacy, gamete intrafallopian transfer and preimplantation genetic diagnosis – are remarkable. Improved take-home-baby rates, fewer multiple pregnancies, lower rates of ovarian hyperstimulation syndrome, and time-lapse embryology have followed. This rate of advancement likely reflects our societal drive to develop these technologies, with corresponding improvement in outcomes as described in this issue. The next 40 years are likely to be exciting. None declared. Completed disclosure of interests form available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Genes and male infertility: what can go wrong?

Background: To evaluate obstetrical and neonatal outcomes of singletons conceived after advanced assisted reproductive technology (ART) techniques: conventional IVF pregnancies (C-IVF), ejaculated sperm intracytoplasmic sperm injection (ICSI), assisted oocyte activation (AOA), in vitro maturation (IVM), and testicular sperm extraction (TESE). Methods: The subjects were 3,028 singletons who were born after fresh or frozen embryo transfer. The subjects were separated into five groups: C-IVF ([Formula: see text]), ICSI ([Formula: see text]), AOA ([Formula: see text]), IVM ([Formula: see text]), and TESE ([Formula: see text]). We evaluated obstetrical and neonatal outcomes calculating the adjusted odds ratio (AOR) using multivariable logistic regression analyses for fresh and frozen embryos and for cleavage and blastocyst transfer. The C-IVF group was used as a background control for the ICSI group. Moreover, the TESE, AOA, and IVM groups were compared to the ICSI group to evaluate the effects of the ICSI procedure itself. Results: The incidence of perinatal complications was significantly lower in the ICSI-fresh group ([Formula: see text], 95% CI: 0.10–0.83, [Formula: see text]). Regarding sex ratio, the IVM was significantly associated with sex ratio imbalance toward female in both fresh and frozen groups ([Formula: see text], 95% CI: 0.10–0.96, [Formula: see text], 95% CI: 0.07–0.98, [Formula: see text]). On the other hand, there were no significant differences in preterm birth rate, low birth weight rate and congenital abnormalities rate between conventional IVF, ICSI, and the other groups. Conclusions: There were no negative effects on obstetrical and neonatal outcomes between conventional IVF and ICSI. Although this was a limited sample size study, advanced ART technologies such as AOA, IVM, and TESE also seem to have a low risk of adverse impact on obstetrical and neonatal outcomes but may have a slight impact on sex ratio.

Background. Varicocele is a common cause of male infertility, and it may affect the outcomes of ART (assisted reproductive technologies). Surgical treatment of varicocele may increase the likelihood of success of ART, but to date there are limited studies evaluating the results of intrauterine insemination (IUI), in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) after varicocelectomy. Materials and methods. We searched, analysed and systematised publications in PubMed and e-Library databases using the keywords «мужское бесплодие», «фрагментация ДНК сперматозоидов», «варикоцеле», «ВМИ», «ЭКО», «ИКСИ», “male infertility”, “sperm DNA damage”, “varicocele”, “IUI”, “IVF”, “ICSI”. 27 publications were included in the review after exclusion of conference abstracts, theses, dissertations and their abstracts. Results. Only 3 controlled studies comparing pregnancy and live birth rates from intrauterine insemination after varicocelectomy and in the absence of surgical treatment were found. Only one of these studies found a statistically significant increase in these rates. The results of most of the studies evaluating the effect of varicocelectomy on the effectiveness of IVF/ICSI were in favor of surgical treatment before the ART procedure. However, the studies were mostly retrospective, which did not allow drawing an unambiguous conclusion. Conclusion. Despite the insufficient number of randomized controlled trials confirming the effect of varicocelectomy on pregnancy and live birth rates during IUI, IVF and ICSI, it is advisable to perform this intervention before using ART.

The introduction of intracytoplasmic sperm injection (ICSI) in 1992 has revolutionized the treatment of male infertility (1) and has allowed couples whose only prior options were donor insemination to achieve pregnancies or adoption. Although in vitro fertilization (IVF) and related procedures have been used in the past for the treatment of male infertility, most assisted reproductive technology centers are using ICSI as the primary treatment for male infertility. Table 1 lists the cause of male factor infertility. Only a small minority of such patients are amenable to specific hormonal or pharmacologic therapy. Of these, the most probable candidates are the 1–2% of men with male infertility secondary to hypothalamic-pituitary (gonadotropin) insufficiency. These patients respond well to gonadotropin or GnRH therapy. Specific medical treatment is not available for most patients with testicular or idiopathic causes of male infertility. These patients are candidates for assisted reproductive technologies using oocytes from their spouses or partners. This article reviews the ICSI procedure, its indications, and techniques used to retrieve sperm and the risks and concerns that have been raised in regard to its safety, including the genetic risks to the fetus.

Background: Although the number of patients receiving vasoepididymostomies is gradually increasing, these individuals are limited in the recent advanced assisted reproductive technology (ART) era. A novel technique involving vasoepididymostomy with epididymal tubular invagination has been reported. We attempted to define the results of this method and to compare them with the conventional end-to-side technique in patients with suspected epididymal obstruction and no previous history of vasectomy. Methods and Results: Eight eligible triangulation end-to-side vasoepididymostomy procedures performed on five azoospermic patients exhibiting either unilateral or bilateral epididymal obstruction are described. The overall patency rate following operation was 100% (five of five). Two pregnancies were achieved by natural intercourse and one was accomplished via artificial insemination. A single pregnancy was obtained with an intracytoplasmic sperm injection using frozen-thawed sperm collected during the operation. Conclusion: Vasoepididymostomy, using the triangulation technique for epididymal obstruction, resulted in an earlier patency in all patients. This method may afford advantages when compared with the conventional end-to-side approach; however, larger subject populations are required in order to assess further the efficacy of this procedure. In addition, long-term follow up is necessary. (Reprod Med Biol 2003; 2: 101-104).

Do assisted reproductive technologies cause adverse fetal outcomes?