Seizures in paediatrics as a big cause of morbidity.pptx

Seizures

1. MANAGEMENT OF AN INFERTILE COUPLE PRESENTERS; NABATANZI RITAH TUGUME FRANCIS TUTOR; DR ADROMA MOSES

2. CONTENTS Definitions Causes of infertility Investigations Management

3. Definitions Infertility ; Inability to conceive after one year of regular and unprotected sex. Fecundability ; Is the probability of conceiving in 1 menstrual cycle. Average is 20 %, maximum is 35%. At the end of one year trial 85 to 90% will conceive. Fecundity ; physiologic potential to produce offspring Fertility ; Actual number of children born to a woman. Earlier evaluation done when; History of prior infertility Presence of obvious risk factors Age of woman greater than 35

4. Epidemiology In Uganda; 10-15 % of the couples cannot have children. 75% is due to STIs. World; In the U.S, it affects 9% and 10% of men and women respectively between 15 to 44 yrs of age. 48million couples and 186 million individuals live with infertility globally (WHO). 1 in 4 healthy women in their 20s and 30s will get pregnant in any single menstrual cycle1 in 10 healthy women in their 40s will get pregnant in any single menstrual cycle. Fertility begins to decrease for women in their 20s and 30s and declines more quickly after the age of 35(American college of Obstetrics and gyneacologists ). Couples in which the male partner is 40 years or older are more likely to have difficulty conceiving(CDC, 2019).

5. Classification Primary infertility ; A pregnancy has never been attained before. Secondary infertility ; At least one prior pregnancy has been attained before regardless of the outcome. Basic evaluation of an infertile couple History and examination Husband semen analysis Test of ovulation Test of tubal patency Atleast a TVS

6. Overview of infertility Female 40-55%, Male 40%, Unexplained in 10% Female causes

7. History and examination Female history Age length of time spent trying for pregnancy Any previous pregnancies and their outcomes if any Any abortions History of contraceptive use Coital frequency (frequency, dyspareunia) Occupation (exposure to radiation or chemotherapy, stress) Menstrual history (menarche, LMP, regularity, length of cycles, amount) Previous surgical and medical history (STDs, PID, fibroids, endometriosis, PCOS) (pelvic surgery, tubal surgery, uterine instrumentation) Previous fertilization treatment Cervical smear history History of galactorrhea . Female examination General exam;- BP, Pulse, height and weight, signs of virilisation and hirsutism , visual field testing for bitemporal hemianopia Breast examination;- nipple discharge ( hyperprolactinemia ) Pelvic exam e.g. asses cervix, uterine size, version, tenderness and adnexal masses, fibroids, anteverted fixed uterus

8. Male history Length of time spent trying for pregnancy Sexual history;- frequency and timing. Fathered any pregnancies History of mumps or measles History of testicular trauma or surgery to the testes Occupation;- nature of job and prolonged absence from home, radiations, chemicals and heat Medical and surgical history e.g. chronic disease like DM, renal disease Male examination Testicular examination;- site, volume, consistency, masses, absence of the vas deferens, varicocele , evidence of surgical scars. Gynacomastia Hypospadius PR for prostate

9. INVESTIGATIONS Tests for ovulation Basal body temperature-3 to 4 days after ovulation, rise by 0.4 degrees F Cervical mucus changes estrogen; mucus is thin and stretchable (spinnbarkeit phenomenon), ferning pattern progesterone- mucus thick not stretchable, breaks apart Vaginal cytology; sample taken from lateral vaginal walls near fornix Kinds of cells ; Superficial cells- eosinophillic cells with small pyknotic nuclei, they predominate under influence of estrogen Intermediate cells; predominate under progesterone Parabasal and basal cells- round, large nucleus, small cytoplasm( stains blue)- when there's no hormone stimulus. Karyopyknotic index/cornification index—superficial cells/(intermediate + parabasal cells) Maturation index– Parabasal: intermediate: superficial; during ovulation—0:30:70; the index shifts to the right Endometrial sampling; done 1 week prior to expected menses in luteal/secretory phase (D21 in 28 day cycle), if on D21 there proliferative changes, it means ovulation didn’t occur. D21 serum progesterone; less than 3ng/ml implies anovulation greater than 10ng/ml denotes normal corpus luteum function Urinary LH; ovulation expected to occur 14- 26 hrs after detection of urinary LH surge, helps in timing of sex. Follicular monitoring on ultra sound

10. Follicular monitoring on ultrasound; Dominant follicle grows at 2mm/day, max 20-25 mm After ovulation, it shrinks in size, creates margins, fluid seen in pouch of Douglas. Advantages; monitor treatment ie ovulation induction, see the growth of the endometrium

11. Tubal patency tests Screening- Hysterosalpingography Timing- post menstrual i.e follicular phase D5-D11, usually D10; to prevent disruption of any an unidentified pregnancy. Contraindications Pregnancy Genital TB Active genital infection Dye allergy Bleeding Cannula used; Leech wilkinsons cannula Rubins insufflation cannula

12. Sonosalpingography; SSG or sion test Normal saline into the uterine cavity via Foley catheter. An inflated bulb of the catheter prevents leakage of fluid outside uterine cavity. By visualizing the flow of saline along the tube and observing it as a shower at fimbrial end, tubal patency can be tested. Presence of free fluid in  pouch of Douglas  also confirms tubal patency . Advantages; no radiation Assess the uterus Disadvantages; Difficult to tell which tube is locked Laparascopic chromopertubation (gold standard) Laparascope through the abdomen, methylene blue dye introduced through a cannula into fallopian tube. Direct visualization of dye draining through tube. Advantages: silmutaneous assessment of pelvis.

13. Uterine evaluation USG HSG Saline infusion sonography Gold standard- Hysterosapingography Cervical factor ( not done anymore) Post coital test (Sims Huhner test) Check for cervical mucus characteristics Shaky/ circulatory motility of sperm- Antisperm antibodies present.

14. What happens with reproductive ageing? Ovarian reserve tests D3 serum inhibin D3 serum FSH ; FSH >10IU/L is poor reserve D3 serum estradiol; Basal estradiol >60-80pg/ml is poor reserve D3 antral follicle count; <4 in both ovaries is poor reserve Serum AMH; derived from preantral and small antral follicles which make the ovarian pool hence a direct reflection of residual ovarian pool T esting done anytime of the cycle Low AMH (0.2-0.7ng/ml) is poor reserve. AMH > 1 is normal Clomiphene citrate challenge test

15. Treatment methods Anovovulatory disorders- Ovulation Iinduction Group 1 -Hypogonadotropic hypogonadism- Pulsatile GnRH Therapy Group 2 -Eugonadotropic Eugonadism eg PCOS- Clomiphene Citrate, Letrozole Group 3 -Hypergondotropic Hypogonadism eg POI- Ovum donation Group 4- Hyperprolactinemia; decreases GnRH- Bromocriptine , Cabergoline Clomiphene Citrate Nonsteroidal selective Estrogen Receptor Modulator (SERM) Anti estrogenic action-Blocks estrogen receptors at the pituitary gland This creates a false signal of low estrogen levels In turn FSH increases, promote multi follicular growth-Risk of multiple pregnancy-7-10% No teratogenic effects Dose; 50mg-100mg/day

16. Letrozole Aromatase Inhibitor Inhibits conversion of androgen to estrogen Hence creating an estrogen like deficiency state hence increase FSH and more follicular growth DOC for ovulation induction in PCOS women Dose 2.5 to 7.5 mg/day *5/7 Gonadotropins Earlier- Human Menopausal Gonadotropins (mix of FSH and LH) Now- Recombinant Gonadotropins-purer forms Are IM injectables Risk of multiple pregnancy is higher-30% GnRH analogues like Leuprolide , used in a pulsatile manner to induce ovulation Ovulation induction protocol Ovulation occurs in 36hrs after giving the trigger IUI-36 hrs after giving ovulation trigger

17. What is in vitro fertilization? Stimulation of ovaries Retrieval of oocytes Fertilization- on culture media Embryo formed grows in culture media Embryo transfer-Day 5 embryo transferred in the uterus Indications of IVF Tubal factor infertility Severe male factor infertility Treatment failure Unexplained infertility IVF with donor oocyte IVF with surrogacy IVF with pre implantation genetic diagnosis

18. Infertility in males Introduction Definition Causes of infertility Investigations Management

19. introduction Infertility definition As above, in approximately 35% of couples with infertility, a male factor is identified along with a female factor; in approximately 10%, a male factor is the only identifiable cause

20. Male reproduction summary Anatomy of testis ( p testes): Outer coverings, internal structures(lobules, seminiferous tubules), interstitial tissue, rete testis, efferent ductules Spermatogenesis (sermatogonial phase, meiotic phase, spermiogenesis) Role of supporting cells( Sertoli cells , Leydig cells) and hormonal control(FSH, LH, testosterone) Hypothalamic-pituitary-gonadal axis

21. Male reproduction summary part 2 Male infertility is due to defect in either; Production of healthy sperms Transportation of healthy sperms to site of fertilization Emission( movement of sperm and glandular secretions into urethra in preparation for ejaculation with the end result that urethra is loaded with semen):sexual stimulation of SNS, peristaltic contractions in Vas deferens, seminal vesicles, prostate gland, ejaculatory ducts that deliver sperm and fluids into the prostatic urethras, contraction of internal urethral sphincter Ejaculation( forceful expulsion of semen from urethra to outside):sexual stimulation and somatic reflexes via pudendal nerve, rhythmic contractions of pelvic floor muscles (BS,IC) and urethral muscle, ejection of semen, relaxation of external urethral sphincter) PLUS orgasmic sensations and temporary loss of voluntary control Semen: spermatozoa(5-10%), seminal fluid(about 60%), prostatic fluid(20-30%), bulbourethral (5%) and others. Healthy semen: pH(7.2-8.0),2-6ml in volume, sperm count is 15-200 million sperm/ml, whitish-gray, smells chlorine-like

22. Useful terminology CONDITION TERMINOLOGY No semen Aspermia No sperms Azoospermia Less sperms Less than 15 million /ml Less than 5 million/ml Oligospermia Severe Oligospermia Non motile sperms Asthenospermia Dead sperms Necrospermia Abnormal morphology Teratospermia Increased WBC in sperms Leucocytospermia

23. Causes of male infertility Congenital disorders Acquired disorders Systemic disorders Congenital GnRH deficiency (Kallmann syndrome) Pituitary and hypothalamic tumors(pituitary macroadenoma ,craniopharyngioma) Severe systemic illness Iron overload syndromes Pituitary and hypothalamic infiltrative disorders( sarcoidosis, histiocytosis, tuberculosis, fungal infections) Nutritional deficiencies Multiorgan genetic disorders(Prader-Willi syndrome, familial cerebellar ataxia, etc.) Head trauma, intracranial radiation, surgery Morbid obesity Vascular(pituitary infarction, aneurysm) Hormonal(hyperprolactinemia, androgen excess, estrogen excess, cortisol excess) Drugs(exogenous androgens, opioids and psychotropic drugs, GnRH agonists or antagonists 1. Endocrine and systemic disorders( hypogonadotropic hypogonadism 2% to 5%) VITAMINSABCDEK SPERM COUNT Can be pre-testicular(mainly hormonal),testicular( mainly structural, genetic, infective), post-testicular (obstructions, ejaculations issues)

24. Congenital disorders Acquired disorders Systemic illness Genetic causes of dysspermatogenesis Klinefelter syndrome (XXY) and its variants(XXY/XY, XXXY) Varicocele(large, palp able without Valsalva maneuver) Idiopathic dysspermatogenesis Y-chromosome microdeletions and related disorders cryptorchidism Infections; viral orchitis(mumps, echovirus, arbovirus),granulomatous orchitis(leprosy, tuberculosis), epididymo-orchitis(gonorrhea, chlamydia) Renal failure, hepatic cirrhosis, cancer, sickle cell disease, amyloidosis, vasculitis, celiac disease Autosome and X-chromosome defects 2. Primary testicular defects in spermatogenesis(65% to 80%)

25. Congenital disorders Acquired disorders Systemic illness Genetic causes of dysspermatogenesis Myotonic dystrophy Drugs :Alkylating agents, alcohol, marijuana, antiandrogens,ketoconazole,spironolactone,histamine-2 receptor antagonists, ionizing radiation Mutations causing severe defects in sperm morphology Functional prepubertal castrate syndrome(congenital anorchia) Environmental toxins: Di bromochloropropane, carbon disulfide, cadmium, lead, mercury, environmental estrogens, and phytoestrogens ; smoking ;hyperthermia Androgen insensitivity syndromes Immunological disorders, including polyglandular autoimmune disease and angiosperm antibodies 5-alpha reductase deficiency Trauma Estrogen receptor or synthesis disorders Testicular torsion

26. 3. sperm transport disorders( about 5%) epididymal dysfunction (drugs, infection) abnormalities of the vas deferens (congenital absence, Young syndrome, infection, vasectomy) ejaculatory duct disorders seminal vesicles and prostate 4.Sexual dysfunction(infrequent vaginal intercourse, ED, premature ejaculation) 5. Idiopathic male infertility(different from idiopathic dysspermatogenesis. Here, the infertile man has normal semen analysis and no apparent cause for infertility

27. Evaluation of male infertility history Duration of infertility Fertility in other relationships Medical and surgical history( chronic severe systemic illness, head trauma, surgery) Infections (STIs, Guts, mumps orchitis) Medications Sexual development history(testicular descent, Tanners staging, etc ) History of chemotherapy or radiation Cigarette smoking, alcohol, marijuana and drug use; environmental and occupational exposures Sexual dysfunction or impotence Frequency of intercourse, use of lubricants toxic to sperm Previous infertility testing and therapies Family history of birth defects, intellectual disability , or reproductive failures

28. Physical examination GENERAL APPEARANCE(sexual development, gynecomastia, obesity, pubic hair). Skin for iron overload, Cushing, longstanding testosterone deficiency EXTERNAL GENITALIA( Tanner stage, Scrotal exam( size, consistency, nodularity of testicles, palpation of cord for presence of vas deferens, DRE, Valsalva for varicocele). Testicular volume determination by Prader orchidometry, ultrasound

29. Semen analysis Semen sample is collected after 2 to 7 days of ejaculatory abstinence either by masturbation at health facility or at home and delivered within an hour of collection to lab. Semen analysis is performed by standardized methods in accordance with WHO laboratory manual for examination and processing of human semen. Standard semen analysis has; Semen volume and pH Microscopy for sperm concentration, count, motility, and morphology; debris and agglutination, leukocyte count, immature germ cells

30. PARAMETER VALUE Volume Greater than 1.4 ml (95% CI 1.3 -1.5) PH > 7.2 Sperm concentration Greater than 15 million/ml Sperm count Greater than 39 million/ejaculate (CI 35-40) Sperm morphology Greater than 4% normal most imp (3-9) Total motility > 42%(40-43) Active motility > 30%(29-31) Viability 58% WBC Count, < 1 million/ml Total Round Cells < 5 million/ml

31. Follow up evaluation Endocrine testing : especially for man wil sperm conc <5 million/ml. serum total testosterone, LH, FSH Low testosterone, high FSH and LH ( primary hypergonadotropic hypogonadism (both spermatogenesis and Leydig function affected)) Normal testosterone, normal LH, high FSH( primary hypergonadotropic hypogonadism with seminiferous tubule damage, intact Leydig cells Low testosterone, FSH and LH low or normal( secondary hypogonadotropic hypogonadism. Look for cause e.g. prolactin, iron overload, brain mass hypothyroidism, hypoadrenalism High testosterone, LH, normal FSH; partial androgen resistance Normal testosterone, LH,FSH( majority) further analysis depends on semen analyss Low sperm count, very low LH, very muscular; androgen abuse Scrotal and transrectal ultrasound; especially obstructive azoospermia( normal testicular volumes, serum testosterone,FSH and LH with azoospermia. Also done if vasa deferens not palpable, generally for obstructions, anomalies vasography Genetic tests: Karyotyping and testing for Y chromosome microdeletions with very low sperm cone. Klinefelter syndrome, cystic fibrosis

32. Semen analysis Low volume Low concentration Abnormal morphology(length, width, width ratio, area occupied by acrosome, neck and tail defects) Poor motility NORMAL CONCENTRATION; incomplete collection, partial retrograde ejaculation AZOOSPERMIA Retrograde ejaculation, congenital absence of vas deferens, obstructive azoospermia Immature germ cels indicate disorders of spermatogenesis Increased white blood cells in ejaculate =inflammation/infection, poor semen quality Very high percentage of immobile sperm in ejaculate =ICSI LOW SPERM CONCWENTRATION: Testosterone deficiency AZOOSPERMIA OR SEVERE OLIGOSPERMIA Genital tract obstruction or vas deferens, seminal vesicles absent (physical exam or scrotal/transrectal ultrasound)or obstructed ejaculatory duct(scrotal or transrectal ultrasound)

33. Treatment Having identified cause of infertility, therapy is aimed at correcting reversible etiologies and overcoming irreversible factors Generally, therapeutic interventions for treatment of infertility are drug therapy, surgery and/or procedures such as intrauterine insemination or in vitro fertilization Absolute contraindications to infertility therapy are contraindication to pregnancy or contraindication to the use of the drugs or surgery to enhance fertility The couple is counseled on lifestyle modifications to improve infertility, such as smoking cessation, reducing excessive caffeine and alcohol consumption , and appropriate timing and frequency of coitus Increasing physical activity and avoiding tobacco, marijuana, excessive alcohol intake, and obesity might be useful in optimizing spermatogenesis. Reduce scrotal heat Dietary supplements such as fish oil, antioxidants

34. Endocrine and systemic disorders The underlying disorder is managed to result in eugonadism and improved spermatogenesis and fertility, otherwise gonadotropin replacement therapy is used. For example, if hyperprolactinemia is cause, the hypogonadism might be corrected by lowering serum prolactin conc. NB: isolated use of exogenous testosterone is advised against among hypo-gonadal men especially if still interested in fertility preservation, but otherwise pursue treatments that result in increase of endogenous serum testosterone production Medical therapy only benefits patients with secondary (hypogonadotropic) hypogonadism but not those with primary (hypogonadotropic )hypogonadism who otherwise require ART such as surgical testicular sperm extraction(TESE) and intracytoplasmic sperm injection (ICSI) into female partner's egg

35. Primary testicular defects in sperm production Low serum testosterone, elevated FSH and LH( primary hypergonadotropic hypogonadism) usually have azoospermia . ART is used Normal serum testosterone and LH, high FSH have variable degrees of dysspermatogenesis. ART Eugonadal, infertile men. Normal serum testosterone, FSH, LH. Those with high quantity of abnormal sperms and oligospermia have no clear medical therapy and will benefit from ART. Those with azoospermia should be evaluated for obstructive causes and treated surgically to enhance or restore fertility e.g. surgical excision of a large varicocele or surgical correction of ejaculatory duct obstruction Sperm in ejaculate(vaginal intercourse, ART), spermatids or mature spermatozoa seen only in testicular biopsies especially in primary hypergonadotropic hypogonadism and azoospermia( surgical retrieval) OR no sperm seen in testicular biopsies( no known therapy) Leukospermia is managed with antibiotics, NSAIDs, mast cell blockers, antioxidants

36. Treatment of sperm transport disorders Optimizing sperm transportation to female partners vagina such as optimizing sexual intercourse, treating ED, ejaculatory disorders, obstruction of epididymis and ejaculatory duct. All can also be treated with ART Retrograde ejaculation with oral sympathomimetics Obstructive azoospermia due to obstruction of epididymis or ejaculatory duct can be managed with microsurgical end to end anastomosis of the epididymal duct to epididymal duct or to the vas deferens. Also, ART with ICSI is an option. Vasectomy reversal. Congenital bilateral absence of the vasa differentia is managed with ART

37. Assisted reproductive technologies Intrauterine insemination +/- gonadotropin stimulation of female partner IVF with ICSI(intracytoplasmic sperm injection) Retrieval of sperm( non obstructive azoospermia, Klinefelter syndrome, longstanding azoospermia after chemotherapy), this is by multiple open testicular biopsies with TESE(testicular sperm extraction) or microTESE , testicular or epididymal aspiration. Genetic counseling and testing is important as there is an increased risk of chromosomal abnormalities and congenital malformations in live births following ICSI. Also infertile men with sperm conc. <10 mil,testing for Y chromosomal microdeletion in men with sperm conc <5 mil/ml, and screening for gene mutations associated with infertility ART with donor semen

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