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Transrectal ultrasonography of infertile men.

OBJECTIVE: To determine normal transrectal ultrasonographic anatomy in young men and the frequency of abnormalities in the infertile population. DESIGN: Transrectal ultrasonography was performed upon 30 fertile volunteers and 150 consecutive men referred for male factor infertility. SETTING: A male fertility center. RESULTS: Transrectal ultrasonography was normal in 60% of controls and 53% of infertile group. The frequency of hyperechoic lesions within the prostate was similar in controls (40%) and infertile men (39%). Müllerian duct cysts were present in 11% of the infertile men and none of the volunteers. Rectal exam was normal in all of the men. CONCLUSIONS: Transrectal ultrasonography is more sensitive at detecting abnormalities of the seminal vesicles and prostate than rectal exam. Hyperechoic lesions within the prostate is frequently a normal finding. Müllerian duct cysts are more frequently observed in infertile men and may be a cause of ejaculatory duct obstruction.

Cysts↗

Epidemiology of endometriosis in infertile women.

OBJECTIVE: To assess the epidemiological factors linked to endometriosis in infertile women. SETTING: Academic tertiary hospital. DESIGN: Case-control study. PATIENTS: One hundred seventy-four infertile women with endometriosis and 174 infertile women without endometriosis, all of them studied by laparoscopy. RESULTS: Women with endometriosis and infertility had a higher frequency of cycles < or = 27 days (26.4% versus 16.7%). A trend to a protective effect of smoking was detected. Social class, reproductive history, infertility history, previous abortions, age, family history, age at menarche, and duration of menstrual flow were similar in both groups. CONCLUSION: Cycles < or = 27 days was the only risk factor that seemed to be associated to endometriosis in infertile patients. However, predictive values were low. A trend to a protective effect of smoking was detected.

Adult↗

Controlled trial of high spermatic vein ligation for varicocele in infertile men.

OBJECTIVE: To determine whether high ligation is an effective treatment for infertile men with clinical varicocele. DESIGN: A randomized, controlled trial of high spermatic vein ligation was carried out. The patients were treated and observed for 3 years. SETTING: Infertility treatment clinic and andrology laboratory in a hospital. PATIENTS: Infertile men with abnormal semen analysis because of varicocele only. INTERVENTION: High ligation 1 year postrecruitment (group A) and at the beginning of the study (group B). RESULTS: Among the 20 couples in group A, 2 pregnancies (10%) were achieved within the 1st year of observation period. During the year after high ligation, there were 8 pregnancies (44.4%), and during the 2nd year after high ligation, there were 4 more pregnancies (22.2%). In group B, 15 pregnancies (60%) occurred within the 1st year after operation. Three pregnancies (12%) and 1 pregnancy (4%) occurred during the 2nd and 3rd year, respectively. After operation in all patients of both groups, there was significant improvement in semen parameters, regardless of pregnancy occurrence. The difference in pregnancy rate (PR) between the operated group B and nonoperated group A during the 1st year of study was found to be highly significant. CONCLUSIONS: It is concluded that in a population of infertile men presenting varicocele as the only demonstrable factor of infertility, the varicocele is clearly associated with infertility and reduced testicular function, and its correction by ligation improves sperm parameters and fertility rate. Furthermore, the highest PR in both groups occurred during the 1st year postoperation.

Adult↗

Tubal ostium membranes and their relation to infertility.

OBJECTIVE: To define the clinical significance of tubal ostium membranes. DESIGN: Retrospective multivariate stepwise logistic regression analysis. SETTING: Algemene Kliniek Sint--Jan, Brussels, Belgium. PATIENTS: Three thousand forty-six hysteroscopies on 2979 patients, including 172 with infertility, over a 9-year period. MAIN OUTCOME MEASURES: Presence of tubal ostium membranes, age, infertility, endometrial thickness, and hormonal environment. RESULTS: Tubal ostial membranes were present in 74 (2.5%) patients: they were unilateral in 30 (42.1%) and bilateral in 44 (57.9%). Their presence was independent from hormonal state and from endometrial thickness. The incidence of ostial membranes was significantly higher (9.9%) in patients referred for infertility for unilateral (3.5%) as well as for bilateral presence (6.4%). Only the bilateral form was age dependent. CONCLUSIONS: Tubal ostium membranes may be one of the unknown limiting factors affecting female fertility and thus reducing the monthly fecundity rate. The present data suggest that bilateral and unilateral tubal ostium membranes may have a different clinical significance. The unilateral form is unrelated to age, hormonal state, or endometrial thickness and can be congenital. This form is most clearly related to infertility. The bilateral form is less related to infertility, is found in women of older age, and can be acquired. Further prospective analysis is needed to clarify the pathogenesis and pathophysiology of tubal ostium membranes. Tubal ostium membranes should routinely be looked for when performing a hysteroscopic examination in infertile women.

Endometrium↗

Chromosomal analysis of sperm from men with idiopathic infertility using sperm karyotyping and fluorescence in situ hybridization.

OBJECTIVE: To determine if idiopathic infertile men having oligozoospermia, asthenozoospermia, or teratozoospermia have an elevated risk of transmitting chromosomal abnormalities to their offspring. DESIGN: Sperm chromosomal complements from five somatically normal infertile men were assayed using the human sperm-hamster oocyte fusion system and the disomy frequencies for chromosomes 1, 12, and the sex chromosomes were determined using fluorescence in situ hybridization. SETTING: Infertile men and normal donors were volunteers in an academic research environment. PATIENTS: Five men with the appropriate semen characteristics were recruited among patients concerned about their infertility. INTERVENTIONS: Sperm fused with hamster oocytes resulting in sperm chromosomes or the sperm nuclei were prepared for fluorescence in situ hybridization. MAIN OUTCOME MEASURE: Structural and numerical abnormalities assessed by sperm karyotypes and the disomy frequency determined by fluorescence in situ hybridization analysis. RESULTS: The infertile men showed increased frequencies of numerical abnormalities and total abnormalities as determined by sperm karyotyping. Analysis of sperm nuclei by fluorescence in situ hybridization indicated a significant increase in the frequency of disomy for chromosome 1 and XY disomy. CONCLUSIONS: Sperm from infertile men may contain an increased frequency of chromosomal abnormalities.

Adult↗

Comparison of reoperation for moderate (stage III) and severe (stage IV) endometriosis-related infertility with in vitro fertilization-embryo transfer.

OBJECTIVE: To evaluate the efficacy of reoperation for stage III or IV endometriosis-related infertility versus IVF-ET. DESIGN: Retrospective analysis. SETTING: In vitro fertilization-embryo transfer unit and tertiary infertility clinic. PATIENTS: Twenty-three couples with stage III or IV endometriosis-related infertility undergoing IVF-ET and 18 women undergoing reoperation for stage III or IV disease, both groups undergoing treatment after failed initial surgery to restore fertility. RESULTS: The cumulative pregnancy rate (CPR) after reoperation for stage III or IV endometriosis-related infertility after 3, 7, and 9 months was 5.9 percent, 18.1 percent and 24.4 percent, respectively. The cumulative PR after one and two cycles of IVF-ET with stage III or IV endometriosis was 33.3 percent and 69.6 percent, respectively. The cumulative PR after one cycle of IVF-ET was higher than with reoperation 33.3 percent versus 24.4 percent. After two cycles the cumulative PR was significantly higher than reoperation 69.6 percent versus 24.4 percent. The mean number of oocytes retrieved was 8.5 +/- 4.6, the mean number of embryos was 4.8 +/- 2.9, and the fertilization rate was 64 percent +/- 21.8 percent. The PR per cycle, per oocyte retrieval and per ET was 38 percent, 42 percent, and 44 percent, respectively, with the implantation rate being 16 percent. The live birth rate per oocyte retrieval and per ET was 29.7 percent and 34.4 percent, respectively. No statistically significant difference could be demonstrated with regard to the fertilization, implantation, nor pregnancy or live birth rates, as compared with IVF-ET outcome with tubal infertility. CONCLUSION: If initial surgery fails to restore fertility in patients with moderate (stage III) or severe (stage IV) endometriosis-related infertility, IVF-ET is an effective alternative; reoperation for asymptomatic patients offers little added benefit.

Adult↗

Flow cytometric evaluation of leukocyte subpopulations in the follicular fluids of infertile patients.

OBJECTIVES: To evaluate the leukocyte subpopulations present in follicular fluid (FF) of infertile patients undergoing IVF-ET for tubal factor, idiopathic infertility, and endometriosis. PATIENTS: Sixty patients undergoing IVF-ET with a tubal factor diagnosis (n = 35), idiopathic infertility (n = 13), and endometriosis (n = 12) had their subpopulations of FF leukocytes analyzed by flow cytometry. MAIN OUTCOME MEASURE: Nonblood-contaminated samples of FF were collected under sterile conditions and centrifuged. Cells were labeled with a panel of monoclonal antibodies: anti-CD3, -CD4, -CD8, -CD14, -CD20, -CD45, and -CD56, and analyzed by cytofluorometry. RESULTS: Follicular fluid leukocytes from patients with idiopathic infertility had a significantly higher proportion of T lymphocytes than tubal factor and endometriosis patients. Endometriosis patients had significantly higher proportions of natural killer (NK) cells, B lymphocytes, and monocytes compared with groups of idiopathic infertility and tubal factor. CONCLUSIONS: The differences observed in the leukocyte subpopulations from FF of patients with idiopathic infertility and endometriosis may affect folliculogenesis and oocyte maturation. Moreover, these modifications could be one of the factors altering their fertility.

Adult↗

Age of the female partner is a prognostic factor in prolonged unexplained infertility: a multicenter study.

Among 2,106 couples registered in 12 Canadian infertility clinics, 470 (22.3%) were classed as unexplained infertility after a uniform evaluation of the male ejaculate, ovulation, and tubal patency. The unexplained group included more older female partners; 44% were over 30 years of age at registration in the participating clinics, compared with 36% in other infertility diagnostic groups. The mean duration of infertility was 40.1 months, and the cumulative pregnancy rate was 36.6 +/- 2.9% at 2 years after registration. When the variables were examined with the use of proportional hazards analysis, each additional month of duration of infertility reduced the expected prognosis by 2%, and a history of pregnancy in the partnership improved the prognosis by 80%. Among couples with 3 years or more duration of infertility (cumulative pregnancy rate, 27.5 +/- 3.9%), an additional year in the age of the female partner when conception was first attempted (mean, 26.8 years) reduces the prognosis by 9%.

Adult↗

Increased oxidative deoxyribonucleic acid damage in the spermatozoa of infertile male patients.

OBJECTIVE: To investigate whether a high level of oxidative DNA damage in spermatozoa occurs in infertile male patients and to examine the influence of antioxidant treatments on the levels of this damage. DESIGN: Controlled clinical study and uncontrolled pilot study. SETTING: Department of Obstetrics and Gynecology, Akita University School of Medicine. PATIENT(S): Nineteen infertile male and 17 control patients. INTERVENTION(S): The levels of oxidative DNA damage in spermatozoa of infertile male and control patients were compared. In addition, 14 infertile males were given antioxidants for 2 months. MAIN OUTCOME MEASURE(S): The levels of 8-hydroxy-2'-deoxyguanosine, a form of oxidative damage, in the spermatozoa were determined using high-performance liquid chromatography with electrochemical detection. RESULT(S): The levels of 8-hydroxy-2'-deoxyguanosine in sperm DNA were significantly higher in male infertile patients than in the control patients (1.5 +/- 0.2 versus 1.0 +/- 0.1 per 10(5) deoxyguanosine) and were correlated with sperm concentrations in ejaculates. Antioxidant treatment resulted in significant positive effects on sperm concentrations, with a significant reduction in sperm 8-hydroxy-2'-deoxyguanosine levels (from 1.5 +/- 0.2 to 1.1 +/- 0.1 per 10(5) deoxyguanosine). CONCLUSION(S): Our present data demonstrate an association between the level of oxidative DNA damage in spermatozoa and male infertility and point to the possible use of antioxidants to reduce this damage.

8-Hydroxy-2'-Deoxyguanosine↗

Impact of infertility treatments on the health of newborns.

OBJECTIVE: To measure the use of infertility treatments in the general population and their association with neonatal health. DESIGN: Cross-sectional, population-based study. SETTING: Canton of Vaud, Switzerland; Etude du Developpement des Nouveau-nés (EDEN), a prospective study of chronic childhood conditions. PATIENT(S): Six thousand four hundred seventy-seven live newborns (6,379 pregnancies) delivered of residents of Vaud in the 19 maternity hospitals between 1993 and 1994. MAIN OUTCOME MEASURE(S): Neonatal morbidity, multiplicity, low birth weight, prematurity, intrauterine growth retardation, transfer to intensive care, and length of hospital stay. RESULT(S): Infertility treatments were reported for 2.1% of pregnancies (129 women, 148 newborns) and were associated significantly with adverse outcomes. Population-attributable risks varied from 3%-20%. The outcomes of twins did not differ regardless of whether their mother was treated for infertility. Among singletons, only low birth weight was significantly more frequent when infertility treatments were used. Unadjusted odds ratios for neonatal morbidity were significant only for multiple births (2.56; 95% confidence interval 1.21-5.42). This association was not influenced by maternal characteristics and it disappeared after controlling for sex, gestational age, and birth weight. CONCLUSIONS(S): An independent effect of infertility treatments on neonatal morbidity cannot be ruled out, but most of their impact appeared to be mediated by multiplicity and prematurity. Reducing the number of medically induced multiple pregnancies is the most effective prevention of neonatal morbidity related to infertility treatments. Follow-up studies are needed.

Confidence Intervals↗

Infertility, fertility drugs, and invasive ovarian cancer: a case-control study.

OBJECTIVE: To assess the risk of invasive ovarian cancer among infertile women treated with fertility drugs. DESIGN: A case-control study. SETTING: Nationwide data based on public registers. PATIENT(S): All Danish women (below the age of 60 years) with ovarian cancer during the period from 1989 to 1994 and twice the number of age-matched population controls. Included in the analysis were 684 cases and 1,721 controls. MAIN OUTCOME MEASURE(S): Influence of parity, infertility, and fertility drugs on the risk of ovarian cancer after multivariate confounder control. Risk measure(s): odds ratios (OR) with 95% confidence intervals. RESULT(S): Nulliparous women had an increased risk of ovarian cancer compared with parous women: OR 1.5 to 2.0. Infertile, nontreated nulliparous women had an OR of 2.7 (1.3 to 5.5) compared with noninfertile nulliparous women. The OR of ovarian cancer among treated nulliparous women was 0.8 (0.4 to 2.0) and among treated parous 0.6 (0.2 to 1.3), compared with nontreated nulliparous and parous infertile women, respectively. CONCLUSION(S): Nulliparity implies a 1.5- to 2-fold increased risk of ovarian cancer. Infertility without medical treatment among these women increased the risk further. Among parous as well as nulliparous women, treatment with fertility drugs did not increase the ovarian cancer risk compared with nontreated infertile women.

Adolescent↗

A novel, rapid, and accurate method for detecting microdeletion involving the DAZ gene in infertile men.

OBJECTIVE: To report on a novel, accurate method for detecting microdeletion involving the DAZ gene in infertile men. DESIGN: Retrospective clinical study. SETTING: University Infertility Center of Cochin Hospital, Paris, France. PATIENT(S): Infertile patients (n = 25) consulting our infertility department during 1998. The patient cohort included subjects with nonobstructive azoospermia and oligoasthenospermia. INTERVENTION(S): Blood samples were collected from each subject. MAIN OUTCOME MEASURE(S): DNA analysis using polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE). RESULT(S): We used a new molecular genetic strategy to rapidly identify deletions of the Y chromosome that include the DAZ locus. The experiment consists of amplifying simultaneously exon 4 of the DAZ and DAZLA genes with the use of specific primers that are complementary to intronic sequences of these genes. DGGE was used to separate the two PCR products, with good resolution. In infertile men with a microdeletion of the DAZ gene, this method allows amplification of an internal control when a deletion of that portion of the Yq chromosome is observed on a single amplification. CONCLUSION(S): This PCR-DGGE method for detection of DAZ gene deletion is simple and fast and does not require the use of radioactive elements. Compared with the classic PCR approach, this new method allows the amplification of the DAZLA copy to be used as an effective internal control in infertile men with microdeletion of the DAZ locus. This procedure could be particularly useful in screening for the DAZ locus in the diagnostic workup of nonobstructive azoospermia and severe oligoasthenoteratozoospermia.

Adult↗

Understanding new genetics of male infertility.

PURPOSE: Greater than 10% of couples are unable to achieve pregnancy. In at least 30% to 50% of these infertility cases a male factor abnormality is involved. Genetic defects are believed to be the cause of a significant percent of these abnormalities. In fact, defects causing infertility, such as chromosomal disorders and congenital hypothalamic-pituitary-gonadal axis syndromes, have long been recognized. With the development of gene targeting technologies in animal models many genes required for male fertility in animals are known, contributing to our understanding of the etiology of this important health problem. We present not only recognized genetic disorders associated with male infertility, but also its emerging and previously unrecognized genetic etiologies. MATERIALS AND METHODS: This review is organized to enable the reader to recognize promptly the major types of genetic defects associated with male infertility, their clinical characteristics and appropriate therapeutic approaches. Due to the explosion of current knowledge in this field and to length restrictions the discussion of genetic defects is concise, referencing predominantly review articles relevant to the topic. RESULTS: Assisted reproductive technologies for overcoming sterility resulting from unrecognized etiologies may have important potential consequences for infertile couples and their offspring. CONCLUSIONS: Familiarity with the genes associated with male infertility is essential for the urologist to better understand, diagnose and treat the male factor couple.

Animals↗

Stimulated reactive oxygen species generation in the spermatozoa of infertile men.

To investigate the possible similarities between the reactive oxygen generating systems of the leukocyte and the spermatozoa, and to identify possible biochemical differences between fertile and infertile patients, the effect of various stimulants on the production of reactive oxygen in fertile, fertile with varicocele and infertile patients was examined. Generation of reactive oxygen species by human spermatozoa was examined in 2 patient groups: a fertile group (14), which included 7 patients with a palpable varicocele, and an infertile group (16) composed of 7 patients with a palpable varicocele and 9 who remained infertile 6 months to 3 years (mean 20 months) after internal spermatic vein ligation. Various known stimulants of reactive oxygen generation in leukocytes were used to assess spermatozoal reactive oxygen production. Reactive oxygen species generation was measured by the technique of chemiluminescence. In the infertile group reactive oxygen generation was markedly increased by the calcium ionophore A23187 and the chemoattractants N-formyl-methionyl-leucyl-phenylalanine and complement 5a (p < 0.05). In addition, fertile patients with varicoceles showed significantly enhanced chemoattractant stimulated reactive oxygen generation compared to fertile donors without varicoceles. This finding of a biochemical alteration in the sperm of infertile patients and patients with varicoceles may lend support to the argument for early varicocele repair.

Adult↗

Grief, depression, and coping in women undergoing infertility treatment.

OBJECTIVE: To identify the levels of grief and depression and the coping mechanisms of women with infertility problems who participated in in vitro fertilization (IVF) or ovulation-induction medication. METHODS: Pretest and post-test data were obtained from 50 IVF and 50 ovulation-induction medication patients receiving treatment at two urban infertility centers. RESULTS: Both groups of women experienced measurable levels of grief and depression before, during, and after treatment. Higher scores on the Grief Experience Inventory were found for both groups of women when pregnancy did not occur. Age, reproductive problems, years infertile, financial impact, and number of past IVF cycles were not found to influence the reported grief or depression levels. Women in the IVF and ovulation-induction medication groups used isolation coping behaviors such as self-talk and sleep. CONCLUSION: Because of moderate to high levels of grief and depression, therapeutic counseling may be more effective if initiated before the infertility treatment. Women's present levels of distress and coping strategies should be assessed prior to initiating infertility treatment to provide the patients with opportunities to learn and practice new adaptive behaviors that could enhance their ability to cope with infertility and the associated medical procedures.

Adaptation, Psychological↗

The lack of associations between rheumatoid arthritis and both nulliparity and infertility.

OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease that occurs more commonly in women and frequently onsets in women of childbearing age. Pregnancy often causes disease remission, with a subsequent flare postpartum. Nulliparity may be a risk factor for RA, but the literature does not consistently report this finding. There may be a production of antibodies in women with RA that could lead to infertility, and subsequent nulliparity, but this has not been proved. We wanted to determine whether there was a relationship between nulliparity, infertility, oral contraceptive use, and adverse pregnancy outcome in women with newly diagnosed RA. METHODS: Through a case control study, using a mailed questionnaire, we compared the fertility and pregnancy outcome histories of 34 women between the ages of 19 and 44 years with recent-onset RA with 68 healthy controls matched for age and marital status. The response rate was 97%. A review of the literature also was performed to study the associations between RA and infertility and nulliparity, using Medline searching key references. RESULTS: We found no association between infertility and the onset of RA. Seventy-one percent of women with RA and 68% of controls had been pregnant. There was a trend toward increased nulliparity in these patients, but the result was not statistically significant (odds ratio [OR], 1.4; P<.6). There were no differences in the number of children (2.6 v. 2.7; P<.6) and parity outcomes in the two groups. Age at first pregnancy was younger in the women with RA (22.6 v. 25.5 years; P<.008), but the education level was higher in the controls (P<.0001), which may explain these differences. Oral contraceptive use was lower in the RA women, but more RA women had long-term use (greater than or equal to 5 years), and neither result was statistically significant. Literature review shows that at best, there are weak negative associations between current estrogen use and RA, and no association with nulliparity and infertility. CONCLUSIONS: It appears that infertility, the number of pregnancies, and pregnancy outcome are not strongly associated with the risk of developing RA in women of childbearing age. However, in this study there may have been selection biases in the women with RA and the controls that differentially could have affected their reproductive outcomes. Thus, a true association could have been missed. Most other published studies find no association between nulliparity and RA.

Adolescent↗

Antioxidant activity in the semen of fertile and infertile men.

OBJECTIVES: To evaluate catalase- and superoxide dismutase (SOD)-like activities in the seminal plasma of fertile and infertile men. METHODS: Semen samples were obtained from consecutive men presenting for vasectomy (n = 12) and infertility evaluation (n = 105) at our institution. Catalase-like activity was measured by the decrease in hydrogen peroxide after incubation with seminal plasma. SOD-like activity was measured as the inhibition of nitroblue tetrazolium reduction due to superoxide anion generation by xanthine plus xanthine oxidase. RESULTS: Mean seminal catalase-like activity (+/-SEM) in fertile men was not significantly different from that of infertile men (369 +/- 49 versus 326 +/- 17 U/mL, respectively). Mean SOD-like activity in the semen of infertile men was significantly greater than in the semen of fertile controls (46.7 +/- 1.5 versus 37.0 +/- 2.8 U/mL, respectively, P <0.05). CONCLUSIONS: Our data show that infertile men do not have deficient seminal plasma SOD- and/or catalase-like activity (two key antioxidants). These findings suggest that the high semen ROS levels in some infertile men are likely due to excessive generation of ROS rather than deficient ROS scavenging activity in semen.

Adult↗

Biologic variability of sperm DNA denaturation in infertile men.

OBJECTIVES: To examine sperm DNA denaturation (DD) in fertile and infertile men and assess the variability of conventional semen parameters and sperm DD in repeated semen samples from infertile men. METHODS: Twenty-one consecutive nonazoospermic, infertile men each submitted two semen samples, 2 to 6 weeks apart. We examined semen samples from consecutive fertile men (n = 10) presenting for vasectomy as controls. Standard semen parameters (World Health Organization criteria) and sperm chromatin structure (evaluated by flow cytometry analysis of acridine orange-treated spermatozoa and expressed as the percentage of spermatozoa with denatured DNA) were monitored. RESULTS: Fertile men had a significantly higher sperm concentration and percentage of sperm motility and a significantly lower percentage of sperm with DD than did infertile men (36 +/- 5.2 x 10(6)/mL versus 12.5 +/- 2.2 x 10(6)/mL, 60.0% +/- 5.2% versus 30.1% +/- 4.1%, and 8.9% +/- 1.9% versus 20.3% +/- 2.5%, respectively, P <0.05). The sperm concentration, sperm motility, and percentage of spermatozoa with DD were not significantly different between the first and second semen samples from the infertile men. Sperm DD showed the lowest average within-subject coefficient of variation (SD/mean), followed by motility and concentration (coefficient of variation 21%, 24%, and 35%, respectively). CONCLUSIONS: Our data demonstrate that infertile men have significantly higher sperm DD compared with fertile men and that sperm DD exhibits a low coefficient of variation ( approximately 20%) on repeated assessment. These data suggest that sperm DD has a relatively low degree of biologic variability.

DNA↗