Congenital Cryptorchidism Research Articles

Association of antimullerian hormone with the size of the appendix testis, the androgen and estrogen receptors and their expression in the appendix testis, in congenital cryptorchidism.

Antimullerian hormone (AMH) causes regression of the mullerian ducts in the male fetus. The appendix testis (AT) is a vestigial remnant of mullerian duct origin, containing both androgen (AR) and estrogen (ER) receptors. The role of both AMH and AT in testicular descent is yet to be studied. We investigated the possible association of AMH with AT size, the AR and ER, and their expression in the AT, in congenital cryptorchidism. A total of 26 patients with congenital unilateral cryptorchidism and 26 controls with orthotopic testes were investigated, and 21 ATs were identified in each group. AMH and insulin-like three hormone (INSL3) concentrations were measured with spectrophotometry. AR and ER receptor expression was assessed with immunohistochemistry using monoclonal antibodies R441 for AR and MAB463 for ER. For the estimation of receptor expression, the Allred Score method was used. AMH concentrations did not present significant differences between patients with congenital cryptorchidism and the controls. Also, no correlation was found between AMH, INSL3, and AT length. Allred scores did not present significant differences. However, expression percentiles and intensity for both receptors presented significant differences. Three children with cryptorchidism and the highest AMH levels also had the highest estrogen receptor scores in the AT. No association was found between AMH and the studied major parameters. However, higher AMH concentrations, in combination with higher estrogen receptor scores in the AT, may play a role in cryptorchidism in some children. Larger population samples are needed to verify this observation.

Fertility Potential is Impaired in Boys with Bilateral Ascending Testes.

Ascending testes have been documented to be descended in the scrotum within the first year of life and then reascended. The aim of this study was to investigate to what extent the fertility potential was impaired in boys with such testes compared to the fertility potential of boys with late referral congenital cryptorchidism. A total of 153 consecutive boys underwent bilateral orchiopexy at age 2 to 7 years (median 3.9) between 2011 and 2018. Of the patients 67 were diagnosed with bilateral ascended testes and 86 with late referral bilateral congenital cryptorchidism. We assessed serum levels of inhibin B and gonadotropins and histological parameters, number of germ cells per tubule cross-section and number of type A dark (Ad) spermatogonia per tubule cross-section. All values were compared to our normal material. Number of germ cells per tubule cross-section of boys with ascended testes (median 0.50, range 0 to 2.29) was not significantly higher compared to boys with congenital cryptorchidism (median 0.37, range 0 to 2.57; p=0.11). Mean number of germ cells per tubule cross-section was below normal range in 40 boys with ascending testes (60%) vs 57 boys with late referral congenital cryptorchidism (66%, p=0.40). Biopsies absent of Ad spermatogonia were noted in 31% of boys with ascending testes (21 of 67) vs 34% of boys with congenital cryptorchidism (29 of 86, p=0.76). Serum levels of inhibin B and gonadotropins did not differ between the 2 groups. The fertility potential of boys with bilateral ascended testes was impaired to almost the same level as that of boys with bilateral congenital cryptorchidism and should therefore be surgically corrected as soon as the diagnosis of ascended testes is settled.

Correlation between insulin-like peptide 3 and appendix testis length in congenital cryptorchidism.

The appendix testis (AT) is a vestigial remnant of Müller's paramesonephric duct. Insulin-like 3 hormone (INSL3) is produced in the Leydig cells of the testis. We investigated the possible correlation between AT length and plasma INSL3 concentrations in patients with congenital cryptorchidism (CCO) and patients with hydrocele, who served as controls. A total of 40 patients with CCO and 34 patients with hydrocele and orthotopic testes were investigated. Sixteen patients presented high cryptorchidism and 24 low cryptorchidism. During surgery, AT was identified in 34 patients with CCO (high cryptorchidism:15, low cryptorchidism:19) and 28 controls. Plasma INSL3 levels were measured with a spectrophotometry enzyme immunoassay Elisa sandwich technique. AT was present in 85.0% of the boys with CCO and 82.4% of the controls. A significant positive correlation was found between the AT length and INSL3 concentrations in CCO patients. A longer AT may reflect better testicular function in boys with CCO, since it is correlated with higher INSL3 concentrations.

New insights into the expression of androgen and estrogen receptors of the appendix testis in congenital cryptorchidism.

Background The appendix testis (AT) is the most common vestigial remnant of the human testis. Variations in the presence and expression of AT androgen receptor (AR) and estrogen receptor (ER) have been reported in cryptorchidism. We studied the possible association of AR and ER expression of the AT with cryptorchidism. Methods ATs were resected from 40 boys who underwent inguinoscrotal surgery, (20 patients with congenital unilateral cryptorchidism [UC] and 20 controls with orthotopic testes and hydrocele). AR and ER expression was evaluated with immunohistochemistry, and the percentage and intensity of AR and ER expression were evaluated by the Allred scoring method. AT length was compared between the two groups. Correlation of AR and ER expression was evaluated independently in patients and controls. Results The Allred score for AR trended toward lower values in UC compared to controls (p = 0.193), while ER scores presented statistically significant lower values in UC compared to controls (p = 0.017). No significant difference or trend was found in the expression of both receptors between high and low cryptorchidism (p = 0.981 for AR, p = 0.824 for ER) and for the appendiceal length between UC and controls (p = 0.369). Conclusions The findings of a trend for lower AR expression and a statistically significant lower expression of ER in UC may suggest an association of AR and ER with cryptorchidism and may provide an insight into the process of testicular descent.

Maternal serum concentrations of bisphenol A and propyl paraben in early pregnancy are associated with male infant genital development.

Are maternal serum phthalate metabolite, phenol and paraben concentrations measured at 10-17weeks of gestation associated with male infant genital developmental outcomes, specifically cryptorchidism, anogenital distance (AGD), penile length and testicular descent distance, at birth and postnatally? Maternal serum bisphenol A (BPA) concentration at 10-17weeks of gestation was positively associated with congenital or postnatally acquired cryptorchidism, and n-propyl paraben (n-PrP) concentration was associated with shorter AGD from birth to 24months of age. Male reproductive disorders are increasing in prevalence, which may reflect environmental influences on foetal testicular development. Animal studies have implicated phthalates, BPA and parabens, to which humans are ubiquitously exposed. However, epidemiological studies have generated conflicting results and have often been limited by small sample size and/or measurement of chemical exposures outside the most relevant developmental window. Case-control study of cryptorchidism nested within a prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at 10-17 postmenstrual weeks of gestation from a single UK maternity unit between 2001 and 2009 and 24months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 330 mothers of 334 male infants (30 with congenital cryptorchidism, 25 with postnatally acquired cryptorchidism and 279 unmatched controls) were included in the present analysis. Maternal blood was collected at enrolment, and serum levels of 16 phthalate metabolites, 9 phenols (including BPA) and 6 parabens were measured using liquid chromatography/tandem mass spectrometry. Logistic regression was used to model the association of cryptorchidism with serum chemical concentrations, adjusting for putative confounders. Additionally, offspring AGD, penile length and testicular descent distance were assessed at 0, 3, 12, 18 and 24months of age, and age-specific Z scores were calculated. Associations between serum chemical levels and these outcomes were tested using linear mixed models. Maternal serum BPA concentration was associated with offspring all-type cryptorchidism both when considered as a continuous exposure (adjusted odds ratio per log10 μg/l: 2.90, 95% CI 1.31-6.43, P = 0.009) and as quartiles (phet = 0.002). Detection of n-PrP in maternal serum was associated with shorter AGD (by 0.242 standard deviations, 95% CI 0.051-0.433, P = 0.01) from birth to 24months of age; this reduction was independent of body size and other putative confounders. We did not find any consistent associations with offspring outcomes for the other phenols, parabens, and phthalate metabolites measured. We cannot discount confounding by other demographic factors or endocrine-disrupting chemicals. There may have been misclassification of chemical exposure due to use of single serum measurements. The cohort was not fully representative of pregnant women in the UK, particularly in terms of smoking prevalence and maternal ethnicity. Our observational findings support experimental evidence that intrauterine exposure to BPA and n-PrP during early gestation may adversely affect male reproductive development. More evidence is required before specific public health recommendations can be made. This work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), Newlife the Charity for Disabled Children, the Mothercare Group Foundation, Mead Johnson Nutrition and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. Visiting Fellowship (J.M.): Regional Programme 'Jiménez de la Espada' for Research Mobility, Cooperation and Internationalization, Seneca Foundation-Science and Technology Agency for the Region of Murcia (No. 20136/EE/17). K.O. is supported by the Medical Research Council (UK) (Unit Programme number: MC_UU_12015/2). The authors declare no conflict of interest.

Detection and Treatment of Persistent Mullerian Duct Syndrome With Transverse Testicular Ectopia

The coexistence of persistent Mullerian duct syndrome (PMDS) with transverse testicular ectopia (TTE) is extremely rare. Due to a lack of distinctive clinical features in the early stages, PMDS coexists with TTE is usuallydiagnosed when patients are examined for other diseases,including cryptorchidism and inguinal hernia. We present a case of a 51-year-old man who presented with a recurrent left indirect inguinal hernia for 2 years and right congenital cryptorchidism. The patient was diagnosed as PMDS with TTE by preoperative magnetic resonance imaging and underwent laparoscopic resection of the right transverse ectopic testis and Mullerian duct residues.

Hypogonadism and Cryptorchidism.

Congenital cryptorchidism (undescended testis) is one of the most common congenital urogenital malformations in boys. Prevalence of cryptorchidism at birth among boys born with normal birth weight ranges from 1.8 to 8.4%. Cryptorchidism is associated with a risk of low semen quality and an increased risk of testicular germ cell tumors. Testicular hormones, androgens and insulin-like peptide 3 (INSL3), have an essential role in the process of testicular descent from intra-abdominal position into the scrotum in fetal life. This explains the increased prevalence of cryptorchidism among boys with diseases or syndromes associated with congenitally decreased secretion or action of androgens, such as patients with congenital hypogonadism and partial androgen insensitivity syndrome. There is evidence to support that cryptorchidism is associated with decreased testicular hormone production later in life. It has been shown that cryptorchidism impairs long-term Sertoli cell function, but may also affect Leydig cells. Germ cell loss taking place in the cryptorchid testis is proportional to the duration of the condition, and therefore early orchiopexy to bring the testis into the scrotum is the standard treatment. However, the evidence for benefits of early orchiopexy for testicular endocrine function is controversial. The hormonal treatments using human chorionic gonadotropin (hCG) or gonadotropin-releasing hormone (GnRH) to induce testicular descent have low success rates, and therefore they are not recommended by the current guidelines for management of cryptorchidism. However, more research is needed to assess the effects of hormonal treatments during infancy on future male reproductive health.

Changing Trends in the Referral and Timing of Treatment for Congenital Cryptorchidism: A Single-Center Experience from Bosnia and Herzegovina

BackgroundCryptorchidism is the most common male urogenital tract disorder identified at birth. Treatment delays of cryptorchidism may be associated with significant complications such as subfertility and testicular cancer. The currently recommended age for performing orchidopexy is between 6 and 12 months of age and no later than 18 months. The aim of this study was to investigate the trends in the pattern of referral and age of boys at the time of operative treatment of congenital cryptorchidism at the largest tertiary care center in Bosnia and Herzegovina. MethodsThe study included all boys who underwent orchidopexy for congenital cryptorchidism during two equivalents periods: 2008–2010 and 2015–2017. We assessed the referral age of patients, the age of patients at the time of orchidopexy, laterality of cryptorchidism, position of cryptorchidic testes palpated before surgery, the intraoperative position of cryptorchidic testis, a clinical position of the testis at follow up, and risk factors for late orchidopexy. ResultsIn total, 324 patients with 386 testes underwent orchidopexy for congenital cryptorchidism during the study periods. Of these patients, 62 received a bilateral orchidopexy (19.1%). Total referral age of patients with congenital cryptorchidism was 23 months (range, 4–74.5 months). Total median age at surgery was 24 months (range, 6–74 months). One hundred and eleven patients (28.8%) underwent surgery at less than the age of 12 months, 136 (35.2%) at less than the age of 18 months, and 250 (64.8%) patients underwent surgery after the age of 18 months. The analysis of the observed two periods (2008–2010 and 2015–2017) showed a statistically significant decrease in the mean referral age and the mean age at surgery over the last 5 years (2015–2017) (p = 0.007 and p = 0.003, respectively). ConclusionsCurrent guidelines for timely operative treatment for congenital cryptorchidism have not been fully implemented in Bosnia and Herzegovina but a gradual improvement is evident. The main factor contributing to delays in orchidopexy was delayed or neglected referral by referring physicians. Optimizing the time of orchidopexy will require an improved coordination at all levels of pediatric health care to diminish the long-term consequences of cryptorchidism. Type of studyRetrospective. Level of evidenceIII.

A Comparative Study of Single Scrotal Incision Orchiopexy of Children with Palpable Low-Lying Undescended Testis with Traditional Inguinal Method

Purpose: Undescended testis (UDT) is a developmental defect in which one or both testicles do not arrive in the scrotum. Its prevalence at birth and one year after is 2%–4% and less than 1%, respectively. Currently, surgery is recommended to treat congenital cryptorchidism in order to prevent testicular degeneration. Classic method is performed via incision in inguinal and scrotum and the new method is done via incision in scrotum. Method: Sixty male participants with 65 UDT undergoing surgery were randomly assigned to scrotal incision (n=31) and classic inguinal incision methods (n=34). Patients were followed for 6 months and testicular atrophy, infection, recurrence, and duration of surgery were compared between two groups. Results: Scrotal incision compared to classic incision method had significantly lower duration of surgery (19.06±2.96 minutes vs. 30±10.42 minutes; p=0.002) and recurrence during follow-up (0 vs. 5 cases; p=0.026). There was only one surgical site infection in the scrotal incision method. There were hematoma and post-operative swelling in 13.3% of cases after scrotal incision method. Conclusion: Scrotal incision is an alternative method for the UDT with lower duration of surgery, lower recurrence rate, and better cosmetic results.

Association of In Utero Persistent Organic Pollutant Exposure With Placental Thyroid Hormones.

In utero exposure to persistent organic pollutants (POPs) can result in thyroid function disorder, leading to concerns about their impact on fetal and neonatal development. The associations between placental levels of various POPs and thyroid hormones (THs) were investigated. In a prospective Danish study initially established for assessing congenital cryptorchidism, 58 placenta samples were collected from mothers of boys born with (n = 28) and without (n = 30) cryptorchidism. The concentrations of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), organotin chemicals (OTCs), organochlorine pesticides (OCPs), T4, T3, and rT3 were measured. The associations between placental THs and various POPs were analyzed using multiple linear regression. Five PBDEs, 35 PCBs, 14 PCDD/Fs, 3 OTCs, 25 OCPs, T4, T3, and rT3 were measured. No correlation between THs and the odds of cryptorchidism was found. Several POPs were significantly associated with THs: (1) T4 was inversely associated with BDEs 99, 100, ΣPBDE, and 2378-TeCDD, and positively associated with 1234678-HpCDF; (2) T3 was positively associated with 2378-TeCDF and 12378-PeCDF; and (3) rT3 was positively associated with PCB 81, 12378-PeCDF, and 234678-HxCDF, and inversely associated with tributyltin, ΣOTC, and methoxychlor. These results revealed that POP exposures were associated with TH levels in placenta, which may be a possible mechanism for the impacts of POP exposures on children's growth and development. This study provides new insight into the complexity of thyroid-disrupting properties of POPs. More research is needed to elucidate the biological consequences of POP exposures.

Selecting Infants With Cryptorchidism and High Risk of Infertility for Optional Adjuvant Hormonal Therapy and Cryopreservation of Germ Cells: Experience From a Pilot Study.

Orchiopexy for congenital cryptorchid testes is recommended between ½ and 1 year of age to preserve testicular germ cell maturation. Early operation is not enough to preserve fertility in 22 and 36% of cases. Aim of this study was to set up a protocol for optional adjuvant hormonal therapy after orchiopexy and thereafter cryopreservation of testicular biopsies from infants with bilateral cryptorchidism and high infertility risk. We included 17 boys with bilateral cryptorchidism, normal FSH, and impaired germ cell number per tubular transverse section (G/T) in testicular biopsies at orchiopexy, 7 months to 3½ years old. Postoperatively, optional adjuvant LHRH (kryptocur®) 0.2 mg/0.1 mL 2× every second day in 16 weeks were offered. Ten boys were applicable for age matching according to parent's choice of treatment regime and G/T. Five of them had kryptocur®, and five were controls. Repeat bilateral testicular biopsy evaluation and cryopreservation were offered to all boys 12 months after primary orchiopexy. For cryopreservation, tissue pieces were incubated with a cryoprotectant with a slow program freezing. Two out of five kryptorcur®-treated boys normalized both the average G/T and the number of adult dark spermatogonia (Ad-S). Another kryptocur®-treated boy with initial low G/T and no Ad-S increased the G/T and achieved normal number of Ad-S at time of cryopreservation. In the control group, two patients reached only normal lower range regarding the G/T and the number of Ad-S. None of boys with less than average 0.2 G/T improved significantly, whether they were kryptocur®-treated or not. Based on literature and the present results, we recommend adjuvant LHRH treatment to boys with cryptorchidism and insufficient genuine gonadotropin stimulation at time of surgery, as these patients have high infertility risk. Cryopreservation should be an option in case of treatment failure of adjuvant LHRH. However, to avoid repeat surgery with biopsy, some parents may choose biopsy for cryopreservation at time of the initial bilateral orchiopexy, well informed that the procedure may only be truly indicated in 22 and 36% of the cases.

Association of placental thyroid hormone concentrations with congenital cryptorchidism

Association of placental thyroid hormone concentrations with congenital cryptorchidism

Spontaneous renal hemorrhage secondary to choriocarcinoma in a man with congenital hypospadias and cryptorchidism: a case report and literature review

BackgroundChoriocarcinoma is a rare malignant germ-cell tumour, most commonly found in adult women. It infrequently presents as spontaneous renal haemorrhage (SRH). Genital malformation and SRH secondary to choriocarcinoma has previously been only reported in females. We present what we believe to be the first case of a male patient with genital malformation (hypospadias and cryptorchidism) and SRH at presentation of choriocarcinoma.Case presentationA 25-year-old man presented to the department with intense pain in the right flank region and lower back. Initial investigations showed spontaneous renal haemorrhage, for which an emergency partial nephrectomy was performed. Clinical, radiological, and pathological investigations suggested a diagnosis of testicular choriocarcinoma with metastases to the right kidney, both lungs, and brain. Initial treatment was with a chemotherapy regimen of cisplatin, etoposide and bleomycin and whole brain radiotherapy; however, 6 months after diagnosis the patient developed liver metastasis, after which time the BEP protocol was switched to ITP with oral apatinib. Despite best efforts, the liver and lung metastasis continued to grow and a decision was made to discontinue active treatment and provide only palliative care until the patient passed away.ConclusionChoriocarcinoma is a difficult cancer to diagnose pre-operatively. In male patients with early metastasis, prognosis may be much poorer than in the commoner gestational choriocarcinoma. A multidisciplinary with comprehensive post-surgical intervention is of great importance in the treatment of these patients.

Cryptorchidism in Sweden: A Nationwide Study of Prevalence, Operative Management, and Complications

To review the cumulative prevalence, operative management, and complications of treatment for cryptorchidism in Sweden. A nationwide observational study from longitudinal register data of all Swedish-born boys 0-18 years of age, diagnosed with cryptorchidism from 2001 to 2014. Primary outcomes were occurrence and age at primary surgery. Secondary outcomes included type of procedure and surgical site infection. Of 20 375 boys diagnosed with cryptorchidism in 2001-2014, 12 766 were surgically treated. The cumulative childhood prevalence was 1.8% (95% CI, 1.5-2.0), with a higher prevalence in boys born prematurely, small for gestational age, or with low birth weight. The median age at treatment decreased from 6.2 years in 2001 to 3.4 years in 2014 (P < .001). Still, 94.1% (95% CI, 92.7-95.6) had surgery after the recommended 1 year of age in 2014. Variations in age at surgery between Swedish counties were great (range, 2.9-5.9 years of age). There were no deaths within 30 days after surgery and the frequency of surgical site infection was low (1.4%; 95% CI, 1.1-1.6). The cumulative childhood prevalence of cryptorchidism was high, and complications were rare. Few boys underwent surgery in a timely manner according to clinical guidelines, and standards of care varied considerably across the country. Further research and collective actions are needed to improve the detection and management of congenital cryptorchidism.

Birth outcomes after inadvertent use of category X drugs contraindicated in pregnancy: Where is the real risk?

Öztürk Z, Ölmez E, Gürpınar T, Vural K. Birth outcomes after inadvertent use of category X drugs contraindicated in pregnancy: Where is the real risk? Turk J Pediatr 2018; 60: 298-305. Drugs contraindicated in pregnancy are medicines that should be avoided by pregnant women, since they carry a concern for teratogenicity or there is no indication for their use during pregnancy. It does not mean that exposures to these drugs always cause harm. The aim of the present study was to investigate the risk of adverse outcomes following maternal exposure to the drugs contraindicated in pregnancy. We retrospectively analyzed prenatal drug exposure records of the pregnant patients referred to the clinical pharmacology consultation service in a tertiary-level university hospital from January 2007 until December 2012. Exposures to category X drugs (CXD) contraindicated in pregnancy were evaluated. After the expected date of delivery, we collected data about pregnancy complications and the outcomes. For comparison the women in the exposed group (N=52) were matched with a control group (N=162) of pregnant women without teratogenic exposure. We observed only one baby born with a birth defect (congenital cryptorchidism) in CXD group (2.6%) and four in control group (RR 0.91; 95% CI 0.10- 7.94). The rates of adverse pregnancy outcomes including miscarriage, preterm birth and congenital abnormality were not significantly different from controls. However, the rate of elective termination of pregnancy was higher in women exposed to CXD while pregnant (RR 2.54; 95% CI 1.11- 5.80, p = 0.027). Contraceptive failure and unintended pregnancy are the reasons for inadvertent drug exposure and choosing abortion. The high perception of teratogenic risk among pregnant women may cause terminations of pregnancies. Individual risk assessment and avoiding the phrase `CXD` or `contraindicated in pregnancy` in counseling may help to reduce maternal concerns about medication use in pregnancy.

Value of hormonal therapy for congenital cryptorchidism

Congenital cryptorchidism is one of the most common congenital anomalies of the male genitalia.Early treatment for cryptorchidism can help to reduce the occurence of infertility, testicular cancer and torsion.Because the mechanism of testicular is very complex, the efficiency of drug treatment is only 20%, and the long-term impact has been uncertain.Thus hormonal therapy in cryptorchidism is still controversial.Some progresses in hormonal treatment of congenital cryptorchidism in recent years are reviewed is this article. Key words: Cryptorchidism, congenital; Hormonal therapy; Value

A risk assessment of a common drug using xenograft model.

Congenital cryptorchidism is the most common male reproductive disorders that is manifest at birth. It affects 2% to 9% of newborn boys (1) and the incidence have been reported to increase (2,3). Cryptorchidism confers an increased risk of infertility and testicular cancer in adulthood (3-5). The process of testis descent is dependent on hormones secreted by fetal testis. According to the studies using rat, fetal testosterone deficiency during a critical period in masculinization development leads to male reproductive disorders such as cryptorchidism (6-8). However, the environmental/lifestyle factors that reduce testosterone production have remained elusive, since it is not possible at present to decide whether rodent models mimic hormone secretion in human fetal testis.

Hypocalcaemia, Hypoglycaemia, Macrosomia and Congenital Cryptorchidism in a Male Offspring of a Mother with Overweight and Gestational Diabetes Mellitus

AbstractThis paper reports a case of a male infant born to a 32-year-old multiparous mother with overweight (BMI 28.5kg/m2) and gestational diabetes mellitus (GDM). The mother had fasting hyperglycaemia (range 5.7- 6.0mmol/L) noted at 24 weeks of pregnancy and was managed with diet alone. There is no family history of diabetes mellitus and the mother did not have pre-eclampsia. Physical examination of the infant revealed macrosomia (birthweight, 4600g) and bilateral congenital cryptorchidism. The baby suffered severe hypoglycaemia (blood glucose 1.7mmol/L) and hypocalcaemia (total serum calcium 1.03mmol/L), manifesting with seizures. He was successfully managed with 10% dextrose water and calcium gluconate infusion, using standard protocol. His karyotype is 46 XY. The patient was discharged from admission at the age of 10 days and was referred to the paediatric endocrinologist at the tertiary hospital. By 8 weeks of age, the right testis was noticed to have descended into the right scrotum. At the age of 3 months, the left testis was still not palpable either in the inguinal canal or the scrotal sac. The patient was lost to follow up. Conclusion: Diet-treated maternal overweight in association with GDM could potentially increase the risk for hypocalcaemia, hypoglycaemia, macrosomia and congenital cryptorchidism in the offspring, highlighting the need for physicians to assess for the presence of these morbidities in such infants.

Positive Oct -3/4 and D2-40 Immunohistochemical Expression in Germ Cells and Suspected Histology Pattern of Intratubular Germ Cell Neoplasia in Boys with Cryptorchidism Vanish after the Age of 2 Years.

Introduction Intratubular germ cell neoplasia (ITGCN) is a precursor to testicular germ cell cancer. Adult germ cell cancer immunohistochemical markers may fail to detect ITGCN in prepubertal boys with congenital cryptorchidism, because positive immunohistochemistry is commonly seen in boys younger than the age of 2 years, where most orchiopexies are performed. The aim of the study was to evaluate the diagnostic challenge to differentiate between a histological pattern of ITGCN and a histological pattern with some atypical germ cells and all positive cancer immunohistochemical markers, but no increased risk of malignancy. Materials and Methods Histology sections from 373 testicular biopsies from 289 boys aged 1 month to 2 years operated for cryptorchidism were incubated with primary antibodies including anti-placental-like-alkaline phosphatase, antiOct-3/4, anti-C-kit, anti-D2-40, and in case of repeat biopsy with anti-stem cell factor (SCF) receptor. Results The prevalence of Oct-3/4 and D2-40-positive staining of germ cells in testicular biopsies were in age groups less than 6 months, 100% and 50%; 6-12 months, 60% and 17%; and 1-2 years, 12% and 4%. A 1 year, 1-month-old boy with Prader-Willi syndrome treated with growth hormone had ITGCN in both cryptorchid testes. In another three bilateral nonsyndromic cases, 8 months, 8 months and 1-year-old, a histological pattern in accordance with ITGCN was found. These three boys had a repeat biopsy from both testes performed at the age of 3 years, 4 months, 3.5 years, and 3 years, 10months, respectively. In all cases, the Oct-3/4 and D2-40 positive germ cells turned negative and the histological pattern normalized completely. The primary biopsies had SCF negative germ cells. Conclusion This study is valuable in identifying the age-related change in Oct-3/4 or D2-40 immunopositive germ cells in seminiferous tubules. An ITGCN-like histological pattern in nonsyndromic cryptorchidism will vanish after the age of 3 years. Even when immunohistochemistry is applied, prepubertal ITGCN is so rarely demonstrated in cryptorchid testes, that it is not plausible that ITGCN generally originates during fetal development in cryptorchidism.

Gene Expression Changes Underlying Idiopathic Central Hypogonadism in Cryptorchidism with Defective Mini-Puberty

The whole genome RNA profiling of testicular biopsies by DNA strand-specific RNA sequencing was examined to determine a potential causative role of isolated congenital cryptorchidism in azoospermia and/or infertility in the context of our previously published GeneChip data. Cryptorchid patients, aged 7 months to 5 years and otherwise healthy, were enrolled in this prospective study. During surgery, testicular tissue biopsies were obtained for histological examination and RNA sequencing. Fifteen patients were selected based on the histological results and were divided into 2 groups. Seven were classified as belonging to the high infertility risk (HIR) and 8 to the low infertility risk (LIR) group. Cryptorchid boys in the HIR group lacked transformation of gonocytes into Ad spermatogonia due to impaired mini-puberty. This group of patients will be infertile despite successful surgery. The new important finding was a decreased PROK2, CHD7, FGFR1, and SPRY4 gene expression in the HIR group. Furthermore, identification of multiple differences in gene expression between HIR and LIR groups underscores the importance of an intact hypothalamic-pituitary-gonadal axis for fertility development. Our RNA profiling data strongly support the theory that in the HIR group of cryptorchid boys insufficient PROK2/CHD7/FGFR1/SPRY4 gene expression induces deficient LH secretion, resulting in impaired mini-puberty and infertility. We therefore recommend hormonal treatment for this cohort of cryptorchid boys with defective mini-puberty following a seemingly successful orchidopexy.