endocrine and kidney diseases - salonia

Male Infertility

• The lecture addresses male infertility, beginning with a case of an infertile couple trying to conceive for 24 months.
• A compulsory part of understanding if a patient can be a father is checking WHO parameters for: volume, concentration, total progressive sperm motility, and morphology.
• Semen analysis alone cannot reliably determine a man's fertility.
• Comparing infertile and fertile men shows semen abnormalities in 70% of infertile men versus 30% of fertile men.
• Sperm DNA Fragmentation (SDF) assesses sperm DNA quality.
• Both partners should be evaluated simultaneously for infertility.
• In the example case, the male partner has no significant medical history, and the female has a regular gynecological evaluation, suggesting no female factor.

Key Definitions

• Fertility is defined as successful reproduction resulting in a live birth.
• Total fertility rate is the number of births per woman of reproductive age (15-45). The total fertility rate was 1.46 live births per female in Europe in 2022.
• Couple infertility is the inability of a sexually active, non-contraceptive couple to achieve spontaneous pregnancy within 12 months.
• Primary infertility: couples who have never had a child and cannot achieve pregnancy.
• Secondary infertility: couples who have been able to achieve a child at least once before.
• Couples presenting as 'white marriages' (not sexually active) are not considered infertile.

Primary vs. Secondary Infertility & Pregnancy Loss

• Miscarriage is the spontaneous loss of a pregnancy before the fetus reaches viability.
• Recurrent miscarriage means two or more failed pregnancies.
• Sperm defects can contribute to recurrent miscarriage.
• In most infertility cases, an idiopathic cause is identified.

Responsibility within Infertile Couples

• 50% of infertility cases present with female risk factors.
• 50% are associated with male issues, with 30% being solely male factors like the absence of sperm.
• Mixed situations account for 20% of cases.
• The male contribution to infertility is roughly 50%.

Temporal Trends in Sperm Count

• Sperm concentration has decreased by 50% over the last five decades.
• Sperm concentration and total sperm count are parameters relevant to clinical assessment.
• Factors such as microenvironment, pollution, stress, and job situations may be associated with sperm count decrease.

EAU Guidelines

• Parallel assessment of both partners is important in managing the infertile male.
• All men with fertility problems, including those with abnormal semen parameters, should be examined.

Clinical Case details

• In one case, the couple has been trying to conceive naturally for 43 months.
• They tried two ICSI cycles with no clinical pregnancies.
• The male partner has advanced paternal age with a sperm DNA fragmentation index (SDF) higher than 70%.

Infertility Rates

• About 15% of couples seek medical treatment for infertility.
• Male-associated factors are found in 50% of involuntarily childless couples, often with abnormal semen parameters.

ART and IVF

• Assisted Reproductive Techniques (ART) and In Vitro Fertilization (IVF) may be used in situations of sperm deficiency.
• Up to 15% of couples undergoing IVF/ART do not have initial andrological evaluations.

Sperm Abnormalities

• Qualitative and quantitative sperm alterations may occur, as well as obstructions preventing sperm from exiting during ejaculation.

Male Infertility Causes

• Potential reasons for male infertility include maldescended testes and varicocele.
• Idiopathic infertility occurs in up to 30% of cases.
• General systemic disorders, genetic factors, and comorbid conditions like diabetes and metabolic syndrome also contribute.

Types of Male Infertility

• Idiopathic male infertility involves impaired sperm parameters without specific cause.
• Unexplained male infertility is infertility of unknown origin with normal sperm parameters and partner evaluation.
• Roughly 19% of cases are idiopathic, while 5% are unexplained, according to one cohort study.

New Information

• One case describes a primary infertile couple where the male partner (age 44) has hypertension, pre-diabetes, and a small varicocele. The female partner is 35.
• According to a study, infertile men are less healthy than fertile men.
• Comorbid conditions and non-communicable diseases occur more in infertile men.
• This includes testicular cancer, melanoma, prostate cancer, and leukemia/Myocardial Infarction
• Another case involves a primary infertile couple who are trying to conceive for the last 2 years and where the male (age 45) has recently had a ischemic attack.

Additional Info.

• Metabolic Disturbance: Metabolic syndromes indicate that obesity, hypertension, and hypercholesterolemia can be associated and cause disturbances. Oxidative Stree can be at the of the testis as well as Diabetes, which increases levels of oxidative at the level of the testis which may give out dysfunction. There also other endocrine factors associated. which is the higher was it circumference and BMI, that lower that quality of seamen.

Risk.

• Over or Obese: Can give lower Seaman paramaters. Risk that increase reactive osygen species, increase sperm DNF, and lead to Sexual disfunction of the Leydig.

Key point for Infertility.

19% of pts are infertile due abnormal or undiagnosed parameters, but 5% are unexplained, and we should be testing for self and testicle checks so there's awareness.

Studies and Info. from that

• Can lead to test tumor if the self-irregular/nodule isn't checked-can become important when theres patient that might be cancerous.
• 10% of pts had htn with infertility.

Clinical Case 4

• In first case, couple had 2 failed ICSIS with OAT and elevated FSH
• 2nd Case pt needed help with physical examine where gland was covered cause micturition and Intercourse was unavaiable.

Seamen info

• Seaman analyzation should always follow 1mil+ sperm concentration normal range: if its not can lead into further issues down range.
• If there's low testile volume-low sperm ect, it needs to be done over in 2-5 days for abstence.
• Germ cells should be multipotent to become sperm.
• Interstatil lye cells prod testorone, and myoid cells is all the tubules.

Spermatogenesis

• Should be 3 months after 3 months from division from prim cells from. There should be time in each phase for full maturation in second division-which will result in mature cells. Maturation should happen in semen

Cells in testis

• Sorili- will help in walls of helping for nutrients etc. Helps in Sertoli cells which will increase androgen binding globuin- can assist and promote growth from within when testostrone inside help.
• Important also to stimulate testis vol with gonadotopins.
• Patients volume has to be addressed cause the relationship, and they need to be stimulated with testo

Hormonal values

AMH= only really is a marker against women but test with aspermia can see what happens in sperli cells. Inhibin are produced by soriti. FSH will lower the value of inbibih HPG axis- helps in with leydig cells since testosterone is involved cause LH is involved for the Leydig.

Dysgensus

• Dysgensus is related to testic cancer cause issue in organ ect. Can affect exposure/chems leading from pregnacny- the chem can affect urogencia pathways for development and higher parmater etc.- highier TDs will affect prodcution.
• If opening of penile shaft is at Ventral face/shaft=hyospadiam-If at doorsl=epispada (rare). Anogenital- the the short distance.

Dysngenal

TD affects and assicaotied higher cancer. They have sperm inbalmces and issue with TDS and Spermatogeneis. There also has issues with 25%+ in men-where needs to varacolicheckup and valsavuvru and Pressure is applied within vein and testies

Spermalic

Spersmalic verin opens to the right vertican and the 25% from test so needs check ups.. The treatment needs be all dilated veins surgically. There an associoationeith oxygen levels. There should also some normality if needed.

Hormone Overview

FSH

• Follicle-stimulating hormone (FSH) interacts with Sertoli cells in the testis.
• FSH is essential for spermatogenesis at puberty.
• Increase the number of receptors for LH, another gonadotropin.
• FSH stimulates ABG.
• It promotes the quality and concentration of sperm in semen.
• FSH is important in the ultrastructure of sperm, affecting the nucleus, chromatin and mitochondria.

ABG

• Androgen binding globulin (ABG) increases interstitial androgen concentration.
• ABG is stimulated by FSH.

LH/Testosterone

• Luteinizing hormone (LH) interacts with Leydig cells to promote testosterone production.
• Testosterone must be transported through vehicles like albumin and SHBG, as it cannot flow freely in the blood.
• Leydig cells have LH receptors and produce testosterone.
• Daily testosterone production is 2-10 milligrams.
• The testis produces up to 95% of total testosterone at the peripheral level.
• Reduced testosterone decreases the probability of good spermatogenesis and results in low sperm concentration.

AMH

• Anti-Müllerian hormone (AMH) associates with FSH with a strong negative correlation.
• High AMH in men presenting with azoospermia lowers probability of sperm.
• A normal AMH value is "4.0".

Inhibin

• Inhibin (mostly inhibin B) has two chains (alpha and beta).
• Inhibin is associated with FSH, where higher FSH means lower inhibin B.
• Having very low inhibin B may indicate germ cell aplasia.

Spermatogenesis

Overview

• If total testosterone reduces in concentration, reduces probability of having good spermatogenesis, ending with alow sperm concentration

Sperm DNA Damage

• Sometimes, patients seek medical aid for unexplained infertility, despite normal spermatogenesis processes and sperm parameters.
• Sperm DNA damage or sperm DNA fragmentation.
• Sperm DNA fragmentation is useful to determine unexplained infertility.

DNA Breaks

• DNA is composed of two chains, allowing for single or double-strand breaks.
• Higher numbers of breaks increase DNA fragmentation index, reducing sperm's information quality.
• A value above 20% for DNA fragmentation indicates very poor semen quality.
• Higher sperm DNA fragmentation index lowers the probability of physiological reproductive good outcomes.
• Advanced paternal age is a key risk factor for poor fertilization outcomes because of lower sperm and DNA quality.

Recurrent Pregnancy Loss

• High SDF index prevent OBGYN specialists from starting IVF, in vitro fertilization processes, or any kind of assisted reproductive techniques.
• Higher numbers of fragmented DNA lowers quality of ART processes.
• Recurrent pregnancy loss is an important factor of sperm quality.
• Embryologists performing ART look at the number of DNA fragments to select sperm, to increase ICSI probability.

Clinical Cases

Case #12

• The primary infertile couple has been trying for 24 months.
• The female partner (age 29) has completely normal fertility assessment.
• The male partner (age 31) had delayed puberty with hormonal issues, sparse facial and body hair, a hint of gynecomastia, difficulty gaining muscle mass despite exercise, height of 192 cm, and low testis volume (5 mL).
• First semen analysis: low but normal volume (1.6 mL) with azoospermia, confirmed upon repetition.
• Lab tests: LH within normal range, very high FSH, low testosterone = primary hypogonadism.
• Inhibin B is very low (9pg/mL).
• Genetic tests showed Klinefelter syndrome (47 XXY), no Y-chromosome microdeletions, and negative CFTR gene mutation assessment.

Different Setting Case

• The couple has been trying for 1.8 years.
• The female partner (age 33) had previous micro polycystic ovary, with normal results and a level of anti-mullerian hormone of 4.0.
• The male partner (age 34) had a previous pregnancy with a different female partner + a history of left cryptorchidism with spontaneous descensus at age nine.
• He had bilateral orchipexy plus testicular biopsy showing Sertoli cell and Leydig cell hyperplasia.
• He was treated with testosterone.

Additional Factors

• One of the relevant contraindications of testosterone is that it can cause problem in fathering since the feedback of testosterone could be completely damaged.
• The male partner is a hairdresser so environmental exposure is a factor alongside lower secondary education and Catholic religion
• The second issue is there are a few very small groups of subjects that belong to religion sects, and they are mostly having sexual intercourse within the very same a sect, potentially amplifying genetic problems.
• At semen analysis he had one single sperm in 30 high performance points of evaluation, means cryptozoospermia.
• Lab testing point: he has a primary hypogonadism, a very severe one, but it is even a compensated hypogonadism, indeed, total T is below normal, but it is not zero, but rather he has total T .0.
• From the genetic standpoint, CFTR gene mutation was negative with geneticist showing mosaicism.

Comparison

• Both primary infertile couples have been trying to conceive for an extended time and presented abnormal karyotypes, indicating Klinefelter + mosaic + Kleinfelter cases.
• Both reported primary hypogonadism with very high FSH.
• Klinefelter patients have problems because of hypogonadism that lead to significant issues.

Follow up info.

• Patients with disorders need cognitive problem with frail bones, or musculoskeletal as well

Hormone Check Importance

• In Europe National Health systems are overall not able to cover all cost. The hormonal profile is important and must be analyzed.

• Total testosterone FSHLH should be test within a infertility analysis. Inhibin and AHM should also be tested.

Hypogonadal Points

• Up to 15% of those infertile patients are hypogonadal.

• Anabolic Steroids: Patients who practice using dangerous steroids is very important to advise. In terms of liver control.

Klinefelter syndrome:

• The clinical case involves with an increased FSH and a potentially normal LH testosterone can be decreased

Further hormonal work-up

Prolactin

• Patients may present hyperprolactinemia cause pitary can case tumors or issues and the prolactine will excrete more than needing.
• From the slender point most pts will be low sexual desire.
• Contrast can used and the gland needs be with more imaging for clear assessment.

TSH

• Indicating thyroid dysfunction can cause or come across during fertility

Genetic Assessment

• Pts with large heads and smaller testicles do not know what Klinefelter may have or what they do since diagnosis maybe is not easy.
• Patients should be aware that genetic speaking may be related to disorders and issue.

Semen analysis

Azoopsermia

• There 2 types- obstructive and nono-obstructives. The difference beteen both is the lack of prodcuctio and one doesn't have anything.

Genetic Assessment OA

• It important to acknowledge with present from congentialbilateral absences can may or may not have epidemus.

CAUSE FROM DEFERENTS

• Most Frq mut-f508. This is typicalinhertiied name. This means the that polymorph has high levl with low reduction os szosperma.
• There 3 ofazf- Y micro deletion is Y Chromosome11Q AND PART DAZ

How do you know when its in your

• Not less maxuline they complete normal and notthing may come across semen levels. 10% is chromosome
• Italy related- Father gave name to of springs. This affect deletion. Azf

KLINDERFEITER

• Male - 500 - 600 born may have the problem

Treatment is gondatrops.

Clinical treatment

When to do Microdeletions

Always to do it if sperm levels

if not over 5mlz ml do it

Testis

• Needs removed, not pulp need removed with lay dig

Kallman syndrome

• It associated with kalig - 1 gene , and can't smell often but there also hear loss
• Use chondotropins for these patients it's unusual but they can become important.