Preimplantation Genetic Testing within the Public Healthcare System in Slovenia.

Preimplantation genetic testing (PGT) is the earliest form of prenatal diagnosis that has become an established procedure for couples at risk of passing a severe genetic disease to their offspring. At UMC Ljubljana, we conducted a retrospective register-based study to present 15 years of PGT service within the public healthcare system in Slovenia. We collected the data of the PGT cycles from 2004 to 2019 and compared clinical outcomes for chromosomal and monogenic diseases using different embryo biopsy and testing approaches. In addition, we assessed the extent to which PGT has become the preferred option compared to classic prenatal diagnostics. We treated 211 couples, 110 with single gene disorder, 88 with structural chromosome rearrangement and 13 for numerical chromosome aberration. There were 375 PGT cycles with oocyte retrieval, while embryo transfer was possible in 263 cases resulting in 78 deliveries and 84 children. Altogether, the clinical pregnancy rate per embryo transfer was 31% in 2004-2016 (blastomere biopsy) and 43% in 2017-19 (blastocyst biopsy), respectively. We assessed that approximately a third of couples would opt for PGT, while the rest preferred natural conception with prenatal diagnosis. Our results show that providing a PGT service within the public healthcare system has become a considerable option in pregnancy planning for couples at risk of transmitting a severe genetic disease to their offspring. In Slovenia, approximately a third of couples would opt for PGT. Although the number of cycles is small, our clinical results are comparable to larger centres.

Epidemiology of Taenia solium infection in the Russian Federation in the last 20 years: a systematic review.

Taenia solium is a zoonotic parasite that causes taeniasis and cysticercosis in humans (as final hosts) and cysticercosis in pigs (as intermediate hosts). The Russian Federation (RF) is traditionally considered as endemic for this zoonosis. However, the epidemiological data on T. solium infection have not been reviewed for the past 20 years, in which time dynamic economical and societal changes have occurred in the RF. The aim of this systematic review was to analyse the status of T. solium infection in RF in the 2000-2019 period. A literature search was conducted, which collected published articles, grey literature and official data on the epidemiology of T. solium taeniasis and cysticercosis in the RF published from 2000. From a total of 2021 articles and 24 official reports originally returned by the search, data were extracted from 12 full text articles and 11 official reports. Taenia solium taeniasis was continuously reported in the RF between 2000 and 2019, with a tenfold decrease in the incidence, from 0.2 per 100,000 population in 2000 to 0.023/100,000 in 2019. Also, the number of administrative units where taeniasis was detected continuously decreased. Cysticercosis in pigs had a declining trend after 2006. In conclusion, although decreasing, T. solium infection is still endemic in several regions and suspected to be endemic in most of the RF.

The significance of the pluripotency and cancer stem cell-related marker NANOG in diagnosis and treatment of ovarian carcinoma.

Ovarian cancer is among the most common gynecologic cancers and unfortunately the most common cause of death from gynecologic malignancies. Due to few early symptoms and insufficient screening programs, an early diagnosis of ovarian cancer is very difficult and new biomarkers related to early ovarian carcinogenesis are needed. In the last years a growing scientific knowledge about cancer stem cells and their markers opened a new perspective on screening and early diagnosis of ovarian cancer. The transcription factor NANOG is not only a pluripotency and cancer stem cell-related marker, but also promotes cancer stem cell-like characteristics of tumor, tumor growth, dissemination, immune evasion, and resistance to conventional therapy. The recent data showed that small stem cells resembling very small embryonic-like stem cells are present in the ovarian surface epithelium of adult human ovaries. These cells expressed several genes related to primordial germ cells, germinal lineage, and pluripotency, including NANOG, therefore their involvement in the manifestation of ovarian cancer are not excluded. As majority of cancer cells within a tumor are non tumorigenic, the therapies targeting these cells cause tumor regression, but the survived cancer stem cells regenerate the tumor, so tumor relapse or reoccur. The eradication of cancer actually requires the elimination of cancer stem cells, therefore new strategies in treatment that specifically target cancer stem cells are urgently needed. Although the therapeutic efficacy of targeting NANOG as a cancer treatment method is still in experimental phase, the gene therapy with small interfering RNA or short hairpin RNA have already shown some promising therapeutic potential. The authors can conclude that NANOG represents a promising diagnostic marker and agent for target therapy of ovarian cancer.

Pork as a source of human parasitic infection.

Foodborne zoonoses have been estimated to annually affect 10% of the global population, among which zoonotic parasites constitute an important class of aetiological agents. The major meatborne parasites include the protozoa Toxoplasma gondii and Sarcocystis spp., and the helminths Trichinella spp. and Taenia spp., all of which may be transmitted by pork. The significance of zoonotic parasites transmitted by pork consumption is emphasized by the prediction by the Food and Agriculture Organization of an 18.5% increase in world pork production over the next 10 years. Of all the porkborne parasites, the three 'T' parasites have been responsible for most porkborne illness throughout history; they are still endemic, and therefore are important public-health concerns, in developing countries. Although the risk of porkborne parasites, particularly helminths, may currently be considered insignificant in developed countries, the modern trend of consuming raw meat favours their re-emergence. This paper overviews the main parasites transmitted to humans by pork, and outlines the main lines of prevention.

Human giardiasis in Serbia: asymptomatic vs symptomatic infection.

Despite the public health importance of giardiasis in all of Europe, reliable data on the incidence and prevalence in Western Balkan Countries (Serbia, Bosnia and Herzegovina, Croatia, Montenegro and FYR Macedonia) are scarce, and the relative contribution of waterborne and food-borne, or person-to-person and/or animal-to-person, transmission of human giardiasis is not yet clear. To provide baseline data for the estimation of the public health risk caused by Giardia, we here review the information available on the epidemiological characteristics of asymptomatic and symptomatic human infection in Serbia. Although asymptomatic cases of Giardia represent a major proportion of the total cases of infection, high rates of Giardia infection were found in both asymptomatic and symptomatic populations. No waterborne outbreaks of giardiasis have been reported, and it thus seems that giardiasis mostly occurs sporadically in our milieu. Under such circumstances, control measures to reduce the high prevalence of giardiasis in Serbia have focused on person-to-person transmission, encouraging proper hygiene, but for more targeted intervention measures, studies to identify other risk factors for asymptomatic and symptomatic infections are needed.

Imported parasitic infections in Serbia.

BACKGROUND: Travel to the tropics is associated with a risk of parasitic infection, which is increasing in parallel with the rise in travel to these areas. We thus examined the prevalence and trend in the occurrence of parasitic infections in Serbian travelers. METHODS: A retrospective analysis of the medical records of all travelers returning from tropical and subtropical areas, who presented at the Institute for Infectious and Tropical Diseases in Belgrade between January 2001 and January 2008, was performed. RESULTS: Of a total of 2440 travelers, 169 (6.9%) were diagnosed with a parasitic infection, including malaria in 79, intestinal parasites in 84 (pathogenic species in 30 and non-pathogenic in 54), filariasis in four, and visceral leishmaniasis and fascioliasis in one patient each. Importantly, of the whole series only 583 (23.9%) were symptomatic, of which 19.4% were found to be infected with a parasite. The single pathogenic parasite occurring in asymptomatic patients was Giardia intestinalis. CONCLUSIONS: Parasitic infection causing symptomatic disease among travelers returning from tropical areas to Serbia is not infrequent. In view of the expected increase in travel to the tropics, diagnostic protocols for tropical parasitic diseases should take these data into account.

Risk factors for Toxoplasma infection in pregnant women in FYR of Macedonia.

The aim of the study was to identify risk factors for Toxoplasma gondii infection in pregnant women in FYR of Macedonia. Retrospective analysis of serological and epidemiological data in a series of 235 pregnant women from Macedonia, tested for Toxoplasma infection between January 2004 and December 2005, showed an overall prevalence of infection of 20.4%. Exposure to transmission factors significantly increased the risk of infection (RR = 1.989, 95 % CI = 1.041-3.800, p = 0.037). The single infection transmission factor that was a predictor of infection in the whole series was exposure to soil (RR = 1.946, 95% CI = 1.026-3.692, p = 0.041). Based on prevalence and the established risk factors for Toxoplasma infection in Macedonia, the health education programme as a sustainable measure for the prevention of congenital toxoplasmosis should focus on educating women of generative age to avoid contact with soil (farming, gardening), and/to adhere to strict hygienic practices afterwards.

Toxoplasmosis in Serbia: time for an action plan.

Known for a century, Toxoplasma gondii has been studied in Serbia half this time, ever since the introduction of the Sabin-Feldman test at the Institute for Medical Research (IMR) in 1959. However, despite 50 years of continuous efforts, exact data on the frequency of acute clinical disease, acute infections in pregnancy and congenital infection in the offspring are still lacking, due to the vague regulatory provision that toxoplasmosis is subject to reporting "in case of epidemiological indications". It is, however, clear that the major Toxoplasma-induced public health issue in Serbia, like elsewhere in Europe, is congenital toxoplasmosis (CT). Continuous monitoring of particular patient groups showed a dramatic decrease in the prevalence of infection over the past two decades, and a consequently increased proportion of women susceptible to infection in pregnancy, suggesting a potential increase in the incidence of CT. Studies of risk factors for infection transmission have provided data to guide national health education campaigns. It is expected that the recent appointment of the National Reference Laboratory for Toxoplasmosis as the focal point for the collection of data from the primary level, will provide the means for accurate assessment of the measure of the problem, which is a prerequisite of an evidence-based nation-wide prevention program. In the meantime, health education of all pregnant women, focused at risk factors of major local significance, is advocated as a sound and financially sustainable option to reduce congenital toxoplasmosis.

Septate, subseptate and arcuate uterus decrease pregnancy and live birth rates in IVF/ICSI.

A retrospective matched-control study to evaluate the effect of uterine anomalies on pregnancy rates after 2481 embryo transfers in conventionally stimulated IVF/intracytoplasmic sperm injection (ICSI) cycles. The study group of 289 embryo transfers before and 538 embryo transfers following hysteroscopic resection of a uterine septum was compared with two consecutive embryo transfers in the control group. Groups were matched for age, body mass index, ovarian stimulation, embryo quality, IVF or ICSI and infertility aetiologies. Number of embryos transferred, embryo quality and absence of uterine anomalies significantly predicted the pregnancy rates in the study group: odds ratios (OR) 1.7, 2.6 and 2.5, respectively (P<0.001). Pregnancy rates after embryo transfer before hysteroscopic metroplasty were significantly lower, both in women with subseptate and septate uterus and in women with arcuate uterus compared with controls. If two or three embryos with at least one best-quality embryo were transferred, the differences were 9.6% versus 43.6%, OR 7.3 (P<0.001) and 20.9% versus 35.5%, OR 2.1 (P<0.03), respectively. Differences in terms of live birth rates were even more evident: 1.9% versus 38.6%, OR 32 (P<0.001) and 3.0% versus 30.4%, OR 14 (P<0.001). After surgery, the differences disappeared. This retrospective matched control study evaluated the influence of septate, subseptate and arcuate uterus on pregnancy and live birth rates after 2481 in conventionally stimulated IVF/intracytoplasmic sperm injection (ICSI) cycles. The study group included 827 embryo transfers (289 embryo transfers before and 538 embryo transfers following hysteroscopic resection of uterine septum ans was compared with two consecutive mebryo transfers in the control group. Both groups were matched by age, body mass index, stimulation protocol, quality of embryos, use of IVF or ICSI, and infertility aetiologies. Multivariate logistic regression analysis of the study group showed that the number of embryos, embryo quality and the absence of uterine anomalies significantly predicted the pregnancy rates: odds ratios (OR) 1.7, 2.6, and 2.5, respectively (P<0.001). The pregnancy and live birth rates before surgery were lower compared with controls, both in women with subseptate or septate uterus and in women with arcuate uterus. If two or three embryos with at least one best quality embryo were transferred, the differences in terms of pregnancy rates were 9.6% versus 43.6%, OR=7.3 (P<0.001) and 20.9% versus 35.5%, OR=2.1 (P<0.03), respectively. The differences in terms of live birth rates were even more evident: 1.9% versus 38.6%, OR=32 (P<0.001) and 3.0% versus 30.4%, OR=14 (P<0.001). After surgery, the differences disappeared. Negative impact of uterine anomalies on pregnancy and on live birth rates are two important arguments for treating uterine anomalies in infertile women.

The outcome of singleton pregnancies after IVF/ICSI in women before and after hysteroscopic resection of a uterine septum compared to normal controls.

OBJECTIVE(S): To evaluate the effect of hysteroscopic resection of a large uterine septum (Class V according to the American Fertility Society (AFS) classification) and of a small partial uterine septum (Class VI according to AFS classification or arcuate uterus) on the abortion rate in pregnancies after IVF and ICSI. STUDY DESIGN: The retrospective matched control study included 31 women who conceived following IVF or ICSI before hysteroscopic resection of a large (12 women) or small partial (19 women) uterine septum and 106 women who conceived following IVF or ICSI after hysteroscopic resection of a large (49 women) or small partial (57 women) uterine septum. For each pregnancy in the study group, we found two consecutive pregnant control women from the IVF/ICSI registry who had a normal uterus and were matched for age, BMI, stimulation protocol and the use of IVF or ICSI and for various infertility causes. The abortion/pregnancy rate was the main outcome measure. Data on the septum length were obtained during hysteroscopic resection by comparing the length of the 1.4 cm long yellow tip of the electric knife to the length of the resected septum. RESULTS: The abortion rate before hysteroscopic metroplasty was significantly higher, both in women with a small partial septum (78.9% before resection vs. 23.7% in the normal controls, OR 12.08) and a large septum (83.3% before resection vs. 16.7% in normal controls, OR 25.00) compared to women with a normal uterus. After the surgery, the abortion rate was comparable to the abortion rate in women with normal uterus: in both women with a small partial and women with a larger septum. CONCLUSION(S): Similar to a large uterine septum, a small partial uterine septum is an important and hysteroscopically preventable risk factor for spontaneous abortion in pregnancies after IVF and ICSI.

Serum beta2-microglobulin as a marker of congenital toxoplasmosis and cytomegalovirus infection in preterm neonates.

BACKGROUND: Fetal serum beta(2)-microglobulin (beta(2)M) has been reported as a reliable indicator of fetal infectious diseases. OBJECTIVES: To evaluate serum beta(2)M as a marker of congenital toxoplasmosis or cytomegalovirus (CMV) infection in neonates. METHODS: beta(2)M was retrospectively measured in 72 neonatal serum samples from preterm neonates. Of these, 32 originated from neonates with serological evidence of congenital toxoplasmosis (n = 12) and CMV infection (n = 20), while 40 samples from neonates in which both infections were serologically excluded served as controls. beta(2)M levels were compared between the infection and control groups. RESULTS: Mean (+/-SEM) beta(2)M levels were significantly higher in the groups of neonates infected with Toxoplasma (5.64 +/- 0.61 mg/l) (p = 0.014) and CMV (6.06 +/- 0.66 mg/l) (p < 0.0001) than in the control group (3.80 +/- 0.2). Against the cut-off level of 5 mg/l, beta(2)M was normal in 36 of the 40 uninfected neonates examined, indicating a specificity of 90%. In contrast, it was elevated in 66.7% (8/12) and 65% (13/20) of the Toxoplasma and CMV-infected neonates, respectively, indicating an overall sensitivity of 66%. CONCLUSIONS: In the absence of urogenital disorders, an increase in beta(2)M in neonates is likely to be infection-induced. We showed that serum beta(2)M is increased in congenital toxoplasmosis and CMV infection in the first weeks of life.

Age, oestradiol and blastocysts can predict success in natural cycle IVF-embryo transfer.

The aim of this study was to evaluate the influence of maternal age and oestradiol concentrations on blastocyst development and live birth rates in natural cycle IVF-embryo transfer. This observational study included 397 natural cycles with IVF embryo transfer for female infertility with embryo transfer on day 5. The cycles were divided into two groups according to the woman's age (<39 and > or = 39 years of age), and into two groups according to oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration (0.4-0.49 nmol/l and 0.5-1.2 nmol/l). Comparison between the cycles in younger versus older age groups showed significant differences in blastocyst development rate, live birth rate per embryo transfer and live birth rate per cycle (55 versus 29%, 23 versus 3% and 13 versus 2% respectively) (P < 0.001). Comparison between cycles with lower versus higher oestradiol concentrations showed no significant differences in blastocyst development rate, live birth rate per embryo transfer and live birth rate per cycle (47 versus 49%, 18 versus 18%, and 11 versus 10% respectively). Advanced maternal age negatively predicts the success of natural cycle IVF, while low oestradiol concentrations on the day of HCG administration (ultrasound criteria fulfilled) do not negatively predict blastocyst development and success of natural cycle IVF.

Comparison of a commercial ELISA with the modified agglutination test for the detection of Toxoplasma gondii infection in naturally exposed sheep.

Surprisingly few commercial ELISAs are available for the detection of Toxoplasma gondii infection in animals, and none for use in sheep have been evaluated. We thus compared the Bommeli Diagnostics ELISA Toxotest for the detection of T. gondii antibodies in ruminants with the reference modified agglutination test (MAT) in a series of 180 sheep sera. ELISA results were analysed at two cut-off levels (30%, comprising both weakly positive and positive results, and 100%, comprising only positive results), and compared with MAT at three cut-off levels (titre of 1 : 25, 1 : 50 and 1 : 100). The results showed a moderate agreement of ELISA at both cut-offs (kappa = 0.46 and 0.51) with MAT at a cut-off titre of 1 : 100. However, the specificity and positive predictive value were above 95% only at an ELISA cut-off of 100%, indicating its potential as a diagnostic test, particularly in areas with a high prevalence of infection. On the other hand, lower sensitivity and negative predictive value limit its value as a screening test. Thus, the ELISA Toxotest may be used for quick diagnosis of T. gondii infection in sheep in the field, i.e. for the differential diagnosis of ovine abortion storms.

Undercooked meat consumption remains the major risk factor for Toxoplasma infection in Serbia.

Toxoplasma gondii infection prevalence and infection risk factors were analyzed in a series of 765 women of generative age from throughout Serbia tested at the Institute for Medical Research Toxoplasmosis Laboratory between 2001 and 2005. The infection risk factors were additionally analyzed in a group of 53 women with acute infection (cases) compared to a group of seronegative women matched for age and education level (controls). The overall prevalence of infection was 33%. Infection risk factors in the whole series were undercooked meat consumption (RR = 1.77, 95% CI = 1.16-2.7, P = 0.008) and exposure to soil (RR = 1.63, 95% CI = 1.17-2.29, P = 0.004), particularly in less educated women. Moreover, undercooked meat consumption was the single predictor of infection in women with acute infection, with an 11-fold increased risk of infection in women who acknowledged consumption of undercooked meat (RR = 11.21, 95% CI = 3.10-40.53, P = 0.000). These data prompted us to analyze the significance of consumption of particular meat types as sources of infection. Of all the meat types mostly consumed in Serbia, only consumption of beef (RR = 1.006, 95% CI = 1.001-1.011, P = 0.027) was shown to influence Toxoplasma infection rates.

Intracytoplasmic sperm injection by testicular sperm in patients with aspermia or azoospermia after cancer treatment.

The aim of this retrospective study was to evaluate the efficiency of testicular biopsy and intracytoplasmic sperm injection (ICSI) in patients with aspermia or non-obstructive azoospermia (NOA) after cancer treatment. From 1996 to 2003, 30 men with a history of cancer, affected by aspermia or NOA and without sperm cryopreserved before cytotoxic treatment underwent testicular sperm extraction (TESE). In these men, clinical, hormonal and histological characteristics were compared; 13 underwent 39 TESE-ICSI cycles using frozen-thawed testicular spermatozoa (TESE-ICSI group). In the same period, 31 ICSI cycles were performed in 20 men with aspermia or NOA using ejaculated sperm frozen before cancer treatment (ejaculated sperm-ICSI group). Fertilization, blastocyst development, pregnancy and miscarriage rates were compared between the groups. Testicular volume, serum follicle-stimulating hormone level and Johnsen score indicated complete although reduced spermatogenesis in men with aspermia and abnormal spermatogenesis in men with NOA. After TESE, sperm retrieval was positive in 92% of men with aspermia and 58% of men with NOA. In TESE-ICSI patients with NOA a significantly lower proportion of embryos developed to the blastocyst stage than in patients with aspermia and in those after ICSI with frozen-thawed ejaculated sperm (23% vs. 43% and 47%, p = 0.03 and p < 0.01 respectively). In all groups the miscarriage rates were high; in patients with aspermia and NOA, characterized by increased age, the miscarriage rate tended to be higher in spite of similar female age and female indications of infertility. In patients affected by aspermia or NOA after cancer treatment and without sperm cryopreserved before treatment, TESE-ICSI using testicular sperm provide a chance to father a child.

Follicular sterol composition in gonadotrophin stimulated women with polycystic ovarian syndrome.

This is the first study evaluating whether oocyte development and fertilization competence are related to intrafollicular concentration of cholesterol, meiosis-activating sterols and progesterone, after human chorionic gonadotrophin (HCG) administration of women with polycystic ovarian syndrome (PCOS). The concentration of follicular fluid meiosis-activating sterol (FF-MAS) significantly increased in the periovulatory period from 10-14 to 34-38 h after HCG administration, while the concentration of testis meiosis-activating sterol (T-MAS) decreased, suggesting a HCG-dependent inhibition of sterol Delta14-reductase. There was no correlation between follicular lanosterol, FF-MAS, T-MAS, and progesterone concentrations and the presence or absence of MII oocytes. Interestingly, free cholesterol level was significantly lower and FF-MAS/cholesterol and progesterone/cholesterol ratios significantly higher in follicles containing MII oocytes compared to follicles from which oocytes were not retrieved. Yet, fertilization and embryo quality did not correlate with follicular sterols. This knowledge should be beneficial for the implementation of protocols for in vitro maturation process, usually used in PCOS patients.

Prolonged HCG action affects angiogenic substances and improves follicular maturation, oocyte quality and fertilization competence in patients with polycystic ovarian syndrome.

BACKGROUND: The aim of this study was to determine whether, in polycystic ovarian syndrome (PCOS) patients, HCG action prolonged for 4 h improves the action of angiogenic substances [ovarian renin angiotensin system and vascular endothelial growth factor (VEGF)], and consequently follicular maturation, oocyte quality and oocyte fertilization competence. METHODS: In this prospective study 20 patients with PCOS undergoing IVF were included. Oocyte retrieval was carried out either 34 or 38 h after HCG administration. Each follicle was analysed for prorenin, active renin, VEGF and estradiol. Oocytes were evaluated for quality (mature, immature, degenerated oocytes), as were the embryos (low or high). RESULTS: In the HCG +38 h group there were 245 follicles, and in the HCG +34 h group 240 follicles. In the HCG +38 h group, log active renin was lower (2.78 +/- 0.20 versus 2.91 +/- 0.25; P < 0.001) and VEGF higher (2276.0 +/- 790.1 versus 1946.6 +/- 954.5 pg/ml; P < 0.001). The odds ratio for obtaining oocytes from follicles was 1.6 [95% confidence interval (CI) 1.1-2.6; P = 0.02], and for developing high quality embryos 7.6 (95% CI 2.8-20.9; P < 0.001) in favour of the HCG +38 h group. CONCLUSIONS: Follicular maturation and oocyte quality are related to the intrafollicular influences of active renin and VEGF in a time-dependent manner after HCG administration, whereas fertilization competence is related to VEGF only.

Blastocyst formation--good indicator of clinical results after ICSI with testicular spermatozoa.

BACKGROUND: The aim of this study was to evaluate the role of blastocyst culture in patients with azoospermia. METHODS: In 98 cycles embryos were cultured for 2 days and in 128 cycles for 5 days to reach the blastocyst stage; a maximum of two of the most developed embryos were transferred in each group. RESULTS: There was a negative correlation between a high (>/=20 IU/l) male serum FSH and embryo development, manifested as embryos not reaching the morula stage on day 5 (r = 0.387; P < 0.05). After prolonged culture, 23% of embryos reached the blastocyst stage. The pregnancy rates per transfer, and the abortion rates were approximately the same in the day 2 group and the day 5 group (20 versus 20% and 19 versus 18% respectively). After blastocyst transfer, a high clinical pregnancy rate (55%) and a low abortion rate (6%) were achieved, whereas the transfer of arrested embryos provided a low pregnancy rate (2%) and a high abortion rate (100%). If only blastocysts had been transferred on day 5, the clinical pregnancy rate per started cycle would have been approximately the same in both groups (13 versus 16%). CONCLUSIONS: Blastocyst formation is a good indicator of clinical results after ICSI with testicular sperm.

Germ cell apoptosis in the human testis.

Apoptosis is a widespread phenomena during development. It represents a form of cell death and has a crucial role in tissue homeostasis. Apoptosis is also involved in a number of pathological conditions. Spermatogenesis is a dynamic process of germ cell proliferation and differentiation. During regular spermatogenesis, the number of testicular germ cells degenerate by an apoptotic process. The significance of regulating cell population by apoptosis is more apparent when sperm production is halted. The presence and frequency of apoptosis in germ cells of human testis biopsy specimens were tested. The results confirm the presence of germ cell apoptosis but not the apoptosis of Sertoli cells. The increased apoptotic index was observed in patients with azoospermia in comparison with normal but obstructed spermatogenesis.