Klinefelter Syndrome And Fertility

Similar results have been reported in studies on patients with nonmosaic KS. Okada et al. (88) reported a decrease in serum testosterone concentration which did not improve after 12 months, whereas a recovery in serum testosterone to 50% of baseline after 12 months was reported in another study (89). Similar results have been published by Ishikawa et al. (90).

Results based on comparisons between the two groups must be interpreted with caution. STUDY DESIGN, SIZE, DURATIONAn extensive literature search was conducted, searching Pubmed, Embase, Cinahl and Web of Science from origin until April 2016 for ‘Klinefelter syndrome’ and ‘fertility’ and various synonyms. Titles and abstracts have been scanned manually by the authors for eligibility. TheEunice Kennedy Shriver National Institute of Child Health and Human Development provides information about research activities and scientific advances relating to Klinefelter syndrome. Most men with Klinefelter syndrome produce little or no sperm, but assisted reproductive procedures may make it possible for some men with Klinefelter syndrome to father children.

Interestingly, no embryo with 47,XXY from KS couples was identified. Analyzing the autosomes separately, the difference was only significant for chromosomes 18 and 21 with both monosomies 18 and 21 and trisomies 18 and 21 present. Overall, 54.0% of the embryos from KS couples were normal with an almost equal sex ratio. Longitudinal measures of testicular volume by palpation in 79 untreated nonmosaic KS patients. Repeated measures in the same patient are connected by a blue line.

This is in accordance with the concept of a progressive degradation of the spermatogonia, and based on single case reports, declining spermatogenesis with ageing in Klinefelter men has been reported (9, 10). In addition, one study found a positive predictive value of testicular volume, testosterone levels and response to hCG test for successful TESE (62), but this association was not confirmed in others (66, 70, 84). Furthermore, no association between outcome of TESE and testicular ultrasonography, intratesticular blood-flow resistance, or degree of virilization has been found (66, 70, 84).

Most boys with Klinefelter syndrome can have sex when they become men, usually with the help of testosterone treatment. However, problems with their testicles prevent them from making enough normal sperm to father children. Boys who have Klinefelter syndrome are born with it. It's also called XXY because they have an extra X chromosome in most or all of their cells. The XXY condition that causes Klinefelter syndrome can't be changed, but medical treatment and working with therapists can help a boy's development and help lessen the condition's effects.

However, the existing results are contradicting and no single parameter has been identified so far. Infertility in KS is a consequence of germ cell degeneration that commences already in utero, progresses slowly during infancy and early childhood, and accelerates during puberty and adolescence, eventually resulting in extensive fibrosis and hyalinization of the seminiferous tubules and hyperplasia of interstitium in the adult patient (for review see (14)). Testicular volume is significantly reduced in infants and prepubertal boys with KS as compared with similarly aged healthy boys (15, 16), indicating that the number of seminiferous tubules is significantly reduced before puberty. More recent studies are more modest in their results, apart from detecting massive fibrosis and hyalinization, which are found in all men suffering from Klinefelter's Syndrome, showed spermatogonia in 4 of the 22 men, with sperm differentiation in 2 of them. In certain studies published, sperm was retrieved in almost 50% of patients and the pregnancy rate after ICSI was no different than that of cycles carried out for other types of sperm insufficiency.

Another approach called in vitro maturation is still experimental and not yet proven to be safe in humans. Despite great achievements in animal studies, no complete in vitro spermatogenesis has yet been accomplished in humans (Wyns, 2010; Aponte et al., 2013). A study investigating in vitro maturation of human germ cells from non-obstructive azoospermic patients showed proliferation of spermatogonia and the differentiation of elongated spermatids. But the spermatids had a low fertilization potential and almost all derived blastocysts showed severe chromosomal aberrations (Sousa et al., 2002). To our knowledge, four studies have been published reporting sperm recovery attempts by ejaculation in adolescents and young adults with KS (TableII).

The micro-TESE technique has proved superior to TESE with respect to minimizing the damage to the testicular tissue, and maximizing the success rate of sperm retrieval (55). Until recently, infertility was considered an untreatable condition in KS.

Repeated measures in the same patient are connected by a blue line. Black lines represent mean±2 s.d . in healthy Danish boys (110). Mean testes volume in adults is indicated by the black line in the right side of the figure (modified from (5)). Even if the conception of 47,XXY pregnancies has been reported (61, 109) it appears relatively safe, but preimplantation genetic diagnosis (PGD) is generally offered to couples with KS who undergo successful TESE and ICSI.

Since Klinefelter syndrome can be hard to notice, many parents don't know their son has it until he grows up or shows delays in puberty. Sometimes, parents who are worried about their son's development consult a doctor, and the diagnosis reveals Klinefelter syndrome. This can help, because the earlier a boy is diagnosed with Klinefelter syndrome, the more effective the treatments usually are.

Accordingly, it has been proposed that adults with KS have a substantially higher proportion of hyperhaploid spermatozoa (46,XY and 46,XX) than healthy males (93, 94), giving these males a theoretically increased risk of fathering a child with 47,XXY or 47,XXX (for review see (95)). Furthermore, an increased frequency of autosomal aneuploidy 13, 18, and 21 in spermatozoa from KS has been proposed (52, 93, 96). Importantly, Blanco et al. (97) suggested that the abnormal cells at the primary and the secondary spermatocyte or the spermatid level were arrested, giving rise to a continuous elimination of abnormal cells in the germ cell line along spermatogenesis.

Exclusion of these did not change the success rates.Table 1 Success rates of sperm retrieval with TESE and micro-TESE in patients with Klinefelter syndrome. Cryopreservation of spermatozoa is currently offered to boys undergoing gonadotoxic treatments, which may render them sterile. The success rate of obtaining sperm from masturbation in adolescent boys depends on the degree of pubertal maturation, but also psychological factors influence whether or not it is possible to obtain a semen sample by masturbation.

The underlying mechanism leading to the ejaculation of sperm in about 8% of apparently non-mosaic KS has not yet been revealed. One possibility could be that a blood mosaicism has simply been overlooked, because most frequently only 20–30 lymphocytes are tested.

Its symptoms – extra height, persistent tiredness, reduced bodily hair and small testes – can be difficult to identify, meaning it often goes unnoticed by patients and GPs. Untreated, however, it can lead to reduced testosterone and infertility, and even increased prevalence of testicular cancer. 108 Masuda H Kondoh N Inamoto T Azuma H Katsuoka Y Tawara F Yamashita M . A case report of successful testicular sperm extraction at 31 years and 41 years of age in a man with Klinefelter syndrome .

Most boys aren't likely to have major health problems, but the condition can bring some other challenges later in life. Klinefelter syndrome puts males at greater risk of breast cancer, some other cancers, and some other diseases like type 2 diabetes, varicose veins and problems with blood vessels, problems with sexual function, and osteoporosis (weak bones) later in life. Usually, a person has 46 chromosomes in each cell, divided into 23 pairs, which includes two sex chromosomes. Half of the chromosomes are inherited from the father and the other half from the mother. The chromosomes contain genes, which determine an individual's characteristics, such as eye color and height.

Klinefelter syndrome may adversely affect testicular growth, resulting in smaller than normal testicles, which can lead to lower production of testosterone. The syndrome may also cause reduced muscle mass, reduced body and facial hair, and enlarged breast tissue. The effects of Klinefelter syndrome vary, and not everyone has the same signs and symptoms. Klinefelter syndrome is a genetic condition that results when a boy is born with an extra copy of the X chromosome.

Based on the existing literature, we here report an average sperm retrieval rate of 50%, ranging from an average of 42% by the use of TESE to an average of 57% by the use of micro-TESE based on studies on a total of 741 males with KS. Although approximately half of cases are successful in retrieving sperm, the reported number of live born children of couples with KS is still limited. Spermatozoa may occasionally be found in the ejaculate, and we therefore recommend always performing analysis of ejaculated semen before considering TESE/micro-TESE. Early androgen replacement therapy in the peripubertal period is generally recommended to allow for normal pubertal development and age-appropriate attainment of muscle and bone mass, although no randomized controlled trial evaluating the effect of this approach exists at present.

Another study by Rohayem et al. investigated the retrieval of spermatozoa by microscopically assisted TESE (mTESE) in a study population of 50 adolescents aged 13–19 years. They reported a spermatozoa retrieval rate of 38% (19/50). However, in the subgroup of adolescents aged 13–14 years, the spermatozoa retrieval rate was 10% (1/10), whereas in the subgroup of adolescents aged 15–19 years the spermatozoa retrieval rate was much higher with 45% (18/40) (Rohayem et al., 2015). Another recent study investigated the spermatozoa retrieval rate by mTESE in 10 adolescents and young men with KS aged 12–25 years and found spermatozoa retrieval rates of 50% (5/10) (Nahata et al., 2016). A recent study by Plotton et al. investigated the effectiveness of TESE in 21 males with non-mosaic KS aged 15–20 years; spermatozoa retrieval rates of 57% (12/21) were achieved (Plotton et al., 2015).

However, with the development of new advanced assisted reproductive techniques such as testicular sperm extraction (TESE) combined with ICSI it seems that KS patients should no longer be labelled as infertile. Especially, microdissection (micro)-TESE has proved to be an advantageous procedure for the identification of testicular spermatozoa in KS. The aim of this review was to describe current knowledge on the testicular changes occurring in KS, the associated changes in reproductive hormones and spermatogenesis, and the existing possibilities of biological fatherhood in 47,XXY patients. In the past 10 years, our knowledge about fertility chances of patients with Klinefelter syndrome (KS, 47,XXY) has changed considerably, especially when regarding the possibility of IVF ICSI treatment (in vitro fertilisation, intracytoplasmic sperm injection) with single testicular spermatozoa.

Boys typically have one X chromosome and one Y chromosome, or XY, but boys with XXY syndrome have an extra X chromosome, or XXY. Infertilty is typically due to severe spermatogenesis impairment responsible for azoospermia in ~90% of men with Klinefelter syndrome (47,XXY) and ~75% of men with mosaic Klinefelter syndrome[4].

Some may be a consequence of the hypogonadism typical for this syndrome, whereas others may be directly related to the chromosome abnormality. Although the vast majority of men with nonmosaic KS are azoospermic, motile sperms in the ejaculate and even spontaneous pregnancies resulting from KS fathers have been described, although such cases are rare (6, 7, 8, 9, 10). In general, Klinefelter mosaics (47,XXY/46,XY) are less severely affected and the chance of finding sperm in the ejaculate in these males is significantly higher than in nonmosaic cases.

Although controversies exist as to whether the HPG axis is impaired in KS infants (16, 33, 34, 35), the latest and largest study on the mini-puberty in KS demonstrated normal testosterone concentrations (35). Importantly, however, the testosterone concentrations were below the median of the controls, which may indicate a subtle Leydig cell dysfunction, although this was not supported by an elevation of LH concentrations (35). This could most likely reflect the fact that androgen receptors are not highly expressed at 3 months and that the normal feedback system is not functioning. Despite the common advice for adolescents with KS to undergo TESE as early as possible as being reported in some literature, we suggest a more expectant approach as previously recommended (Oates, 2012; Gies et al., 2016). Based on the studies described in this work, (pre)pubertal TESE cannot be recommended to date.

Many benefit from extra assistance when it comes to schoolwork. If your son has Klinefelter syndrome, let his teachers and school nurse know about his condition and see what kind of support is available.

In fact, sometimes men aren’t diagnosed with the condition until later adulthood, while seeking treatment for fertility concerns. As little as 15 years ago, there wasn’t much we could do for a man who had experienced infertility as a result of Klinefelter Syndrome. He was thought to be completely sterile and sadly, was treated as such. Chromosomes. They’re the thread-like structures found inside the cells of living organisms.

It has been shown that micro-TESE causes fewer acute and chronic complications than conventional TESE (55, 85, 86, 87). Ramasamy et al. (86) studied 435 patients with NOA without KS undergoing either micro-TESE or conventional TESE and reported fewer acute and chronic changes as evaluated by ultrasound in the microdissection group than in the conventional group. In that study an 80% decrease in serum testosterone at 3–6 months after TESE and an increase to 85% after 12 months and 95% after 18 months was found (86). Klinefelter Syndrome is a condition that has seen miraculous advances on the fertility treatment front over the span of just 15 years.

By the time a child with Klinefelter syndrome is ready to become a dad, there may be new options available related to the extraction of sperm from the testicles. Many boys with Klinefelter syndrome show symptoms related to their development of social and language skills. They may have trouble paying attention. A lot of boys learn to talk late or have trouble using words to express their emotions. They also can have trouble with things like learning to spell, read, and write.

The first case report of a successful TESE in a 15-year-old boy with non-mosaic KS was published in 2001 (Damani et al., 2001). A subsequent study investigated the effectiveness of TESE in 14 boys with non-mosaic KS aged 10–14 years. They found no spermatozoa in the study group, but spermatogonia were found in 50% of the children (Wikström et al., 2004). Another study confirmed these findings by reporting the absence of spermatozoa in all seven boys with non-mosaic KS aged 13–16 years. Again, spermatogonia were found in 4 out of 7 boys (Gies et al., 2012a,b).