بسم الله الرحمن الرحیم

1. بسم الله الرحمن الرحیم • به کانفرانس علمی عقامت خوش آمدید • ترتیب کننده : پوهنمل دوکتور محمد حسن فرید

2. In the name of god Definition : if a young couple did not get pregnancy during one year with at least two time intercourse per week ،without using any contraception method ، means infertility 75 - 80 % of couple got pregnancy in 1 year , 20 - 25 % needs more intervention , but around 10 % of these remained infertile.

3. Most important things for fertility are .. In Men • Normal spermatogenesis production . • Open way for the passage of spermatozoa from testes to the orifice of urethral ( epidydemes , ductus deferent and ductus ejaculatory ). In Women • Normal oovogenesis. • Open way . • Normal development of functional endometrial layer ( compact , spongiosa and basal ) . Any problems interfere in this 5 maintained procedure can change the condition form fertility to infertility . it is effective from 1 - 100 %. absolutely belongs to the intensity ,location , kind of pathology duration and kind of treatment .

4. Percentage of getting pregnancy • 25 % in 1 month after marriage • 63 % in 6 month after marriage • 75 % in 9 “ ‘” “ • 80 % in 12 “ “ “ • 90 % in 18 “ “ “ • 10% rest infertil . • 1/3 cases belongs to the men . • 1/3 = = = women. 1/3 = = = both partner (treatment is verey dificult )

5. Normal semen analysis • Volume 2 - 5 ml ( greish , white or yellow ). • PH 7.2 - 7 .8 . • Sperm count > 20 mil / ml ( 80 - 100 favorable ). • Viability > 50 %. • Morphology > 50 % normal. • Leukocyte < 10 pus cell / ml. • Fructose 13 μ mol per ejaculation .

6. Terminology • Aspermia : No semen. • Azoospermia : Not sperm in the semen. • Oligospermia : Low sperm count . • Asthenospermia : No motile sperm. • Teratospermia : Abnormal sperms .

7. Favorable condition to take semen. • 2 -3 days abstinence intercourse. • Semen take with masturbation . • Within ½ - 2 h must be exam . • Don’t use condom . • 2-3 time should be exam . • Collecting in clean container ( jar )

8. Male infertility factor A – Defective spermatogenesis • Hypothalamus Pituitary failure . • Testicular failure: undesending TesTes, agenesis , cryptorachidism , Damage of the T T by radiation, chemotherapy,orchitis (Mumps,T B,Syphlis)& tumors . • Exposure of T T to heat (NL<2c ). • The T TVaricocle , trauma ,androgen receptor abnormality ,chromosomal abnormality . Enzyme deficiency B - Obstruction in the passage : • Congenital absents of vas . • Block vas due to infection . • Block vas due to herniorrhaphy .

9. C-- Ejaculatory problems • Frequency and timing of intercourse . • Hypospadiasis and phymosis . • Impotence ( erectile dysfunction ). • Premature or retrograde ejaculation. D – immunological problems • Spermal ab. • Cervical mucosa ab.

10. E - Medical diseases • Diabetes , Thyroid disorders • TB , Mumps . • Hypertension. • Intoxication . • Deficiency of vitamins and minerals. F – Other factor • Smoking . • Alcohol. • Drugs . • Environmental. • Age >40 year for male , age > 30 year for female. • Cirrhosis.

11. History • Examination • Semen analysis I-- History • Time of ovulation and frequent coitus on that time. • Coital difficulty like premature and retrograde ejaculation . • Taking drugs like : antihypertensive , antipsychotic , cimetidine ,spirinolacton , oestrogen , excess ( testosterone , smoking , alcohol) and working in hot place can interfere or diminish sperms . 4 Medical illnesses ( D.M , hypertension , thyroid disease , mumps etc ).

12. II - ExaminationA - General • Height : Excess height ( kallman & kalinfelters syndrome ) . • Obesity : Hormonal disorder . • Secondry sex characters examined any abnormality must be noted . • Thyroid gland enlargement . • Medical diseases ( D.M , HP , ect ). Must be palpated by special examination to identify it .

13. B - local examination • Volume of the T.T ( normal 15 – 35 ml) . • Hernia or herniorrhaphy scar . • Hydrocele . • Testicular , descent , volume ,mobility & consistency. • Epididymis ,vas deferent ,Prostate by TR.

14. C - Psychological factor Psychological distress a -fallopian tube spasm Exacerbate angry b –deficiency of g gammete c – decreased coital f frequency d – impotence e - ejaculation p problems Infertility

15. Fertilization • Sperm passes C.R. • Sperm penetrates Z.P by acrosomal reaction & release hyaloronidase ( zonal reaction = ZR ). • Z.R inhibits the entry of other sperm . • Secondary oocyte is formed by second meiotic division mature ovum come out , called female pronucleous . • Within the oocyte the sperm tail degenerated and male pronucleous formed. • pronuclie of male and female mixed and zygote formed with 46 chromosome ( sex belongs to the Y chromosome).

16. Different tests • PCT (Post coital test) : gives information on immunological aspects and cervical mucosa quality . Procedure : Intercourse abstinence 2 -3 days . after intercourse specimen aspirated form cervical canal and posterior fornix separately . 10 or > motile sperm forward movement PCT is ok .abnormal PCT 3 - 5 % . Another specimen collected from posterior fornix acts as a control .

17. Sperm cervical mucus penetration test (S.C.P.T): the semen and C.M placed side by side to form interface . the sperm should penetrated > 3 cm of cervical mucus at the end of 2h (ok ) 3 – sperm cervical mucus contact test (S.C.C.T) : Equal amount of semen and C.M mixed. if > 25 % of sperm show jerky movement after 30 min immunological factor is positive (we need control specimen from the semen) .

18. 4 Other new tests When above 3 mintioned test & semen count are normal the problem may be on fertilization process must be do it: • Zona free egg penetration test : depends upon ability of the sperm to penetrate the zona . free hamster egg more than 10 % penetration considered normal . this test is vary expensive • Acrosin reaction ,sperm zona binding are the new technique to study the fertilizing potential of the sperm. • U/S & Doppler study show scrotal volum and varicocele • Testicular biopsy is indicated in : A - In high F.S.H level primary T.T failure is suspected. B - when TB of the T.T is suspected . C - To study histopathology in presence of oligospermia & abnormal semen parameter . D- In azoospermia to distinguish testicular failure from blockage of the vas deferent or unability of the T T.

19. Advantage of T.T Biopsy • Chromosomal study . • Cryopreservation of spermatids & sperms can be useful in therapeutic. • 5 - intracytoplasmic sperm insemination • ( I.C.S.I ) technology .

20. Management • General . • Hormonal. • Surgical . • New teqnique.

21. 1 - General • Treat the cause . • Improve time & frequency of coitus in the ovulation phase . • Scrotal hyperthermia avoided & use ( cold bath & loose undergarment ). • Limited alcohol and smoking. • Treated medical disorders . • Treated infection with antibiotic • Immunological factor: a – Corticosteroid : 50 mg/d prednisolon. b – use condom 3 - 6 months . the above 2 mentioned things eliminate antibodies 30 - 40 % . c -- Sildenafil ( Viagra ) 25 -100 mg one hour before intercourse, improve erectile function .other method of treatment vacuum pump , local penile implants and local injection . ( have own disadvantage ).

22. 2 - Hormonal therapy • low dose testosterone 25 m g / day improve spermatogenesis ( height dose suppresses ). • Clomiphene citrate 25 mg /d for 25 days in each month for 6 month . • F.S.H / hCG :in pituitary hypofunction. ( FSH 37,5 iu /im twice weekly & increase to 75 iu / im .hCG 2000 iu /im 1 -2 time / weekly continues 6 –12 month ( improvement 60 to 70 %. ( pregnancy 50 - 60 %) . • GnRH 50 ng / kg by intervals within infusion pump or 200 mg / day intranasally in hypothalamus dysfunction. • Thyroid hormones in hypothyroidism. • Bromocryptin in hyper prolactinaemia . Note : these drugs must be used at least for 3 month because spermatogenesis process take 72 days time and passage from the T.T takes 2 weeks more time .

23. 3 - Surgical • Vas vasostomy. • Rectified undescended T.T in child hood (in adult results is not good) . • Surgery of varicocele ( if the sperm count is abnormal ). • Herniorrhaphy .

24. 4 - Newer technologies • Aspermia due to retrograde ejaculation is corrected by giving alpha adrenergic & anticholinergic drugs . Note : urine can be centrifuged & sperm insemination at ovulation time • Artificial insemination ( AI ). • In vitro fertilization ( IVF ) • ICSI ,GIFT , ZIFT & IUI • Micromanipulation technique : such as zona pilloceda dissection , drilling . • Testicular and epidydimal aspiration of sperms when vas is blocked • Donor insemination

25. Detail the newer therapeutic technology in male infertility • AI • IVF. • GIFT. • ZIFT. • Micromanipulation such as zona pillucida dissection drilling . • ICSI. • IUI. Testicular and epididymal aspiration of sperm when vas is blocked .

26. Artificial insemination ( AI) indication: • Impotence & hypospadia . • Premature & retrograde ejaculation . • CMA ( cervical mucosa antibodies) & spermal antibodies . • Oligospermia . • Unexplained infertility .

27. Important factor in female infertility • H.P.O axis factor .(schedul ) • Ovarian factor . • Tubal factor . • Uterine factor. • Cervical mucosal factor . • Vaginal factor . • General factor . 8. Pshycological factor .

28. Ovarian factor • Ovarian agenesis & hypoplasia . • Ovarectomy . • Impaired ovaries function by radiation , infection etc. • Ovarian , cyst. • O.Tumor ( granulosal C T & theaca C T). • Intractable ovaries to effect of GhRH .

29. Suspected ovulation • Monophasic BBT ( must be biphasic ). • Vaginal cytology . • Vaginal PH . • Cervical mucus changes ( fern test +). • Endometrial biopsy ( secretary phase + ). • Level of progesterone in luteal phase .( high + ) • Level of pregnandiol in urine • Level of 17 hydroxy progesterone . • Ostradiol level of plasma. • Saliva glucose level . • Saliva esterase level. • Alkaline phosphates . • Normal and regular cycle ( + ). • Collapse and shrinking follicle . u/s • Collection of fluid in D.G pouch .u/s • Corpus luteum formed. u/s

30. Tubal factor Important function of the tube are : • Transfer released ovum from ovaries to the uterine cavity • Permit entry of the sperm from uterus to the tube . • Transportation zygote onward the uterus . • Creation favorable environment for growth ,development and division of zygote The most important defect of the tube are : • Tubal aplasia & dysplasia . • Tubal blockage congenitally. • Tubal complete or incomplete block by infection disease ,XR & etc . • Bilateral tuballigation . • Tubal adhesion by TB & Chronic PID .

31. Endometrial or uterus factor Rule of the uterus in productive process • Favorable & appropriate environment for zygote , implantation & development . • Protection embryo & fetus from external effect ( trauma , etc ). these following factors are interfere in the process of infertility • Uterus aplasia . • Uterus hypoplasia . • Rudimentary uterus. • Infantile uterus . • Small uterus . • Over retroverted or anteflexed uterus. • Sub mucosal polyps and fibroma . • Acute and specially chronic endometritis. • Destroyed endometrium by radiation ,curettage , chemical or burned material. • Dfd….. • Hysterectomy

32. Cervical factor • Absence of mucus by operation procedure like: amputation of cervix ,cone biopsy & diathermy etc &polyps. • Miss direction like : Retroversion prolapsus of cervix or uterus . • Closed or pin hole cervix .

33. Vaginal factor • Vaginal aplasia . • Vaginal displasia . • Vaginal atrophy . • Vaginal prolapsus &Tomurs . • All kind of vaginitis . General factor Most of medical diseases ( DM , aneamia , vitamins deficiency , hormonal problems .etc ) have own effects on infertility in both partners.

34. Examination • Height and weight . • Secondary sexual organs development. • Hirsutisum and PCOD . • Presence of glactorrhea . • Pelvic examination :( size ,mobility, consistency, location , tenderness , position of the uterus .adnexal masses . Investigation • Menstrual history . • BBT . • Cervical Mucosa Test. • Progestin level . • Endometrial study . • U/S. • Hormonal assay: FSH , LH , Prolactin , thyroid profile.

35. U/S a – Safe ,non invasive & reliable methods . b – Serial u/s monitoring shows growth ,development & rupture of F.du .Graff c – Endometrial growth : Normal endometrial growth before ovulation 8- 10 mm thick. normal growth rate 1 -2 mm /d , reaches around 20 mm or more at ovulation time. After ovulation follicle du graff shrink and fluid can be found in Douglas pouch. d – By u/s we can precise ovulation days . e – dictate administration of hCG . f – Retrieval of ova in IVF process. g – Also recognized PCOD.

36. Explaination • Regular mucus suggest intact H.P.O axis . • BBT explained before . • Serum progesterone level in 22 – 23 days of the cycle 10 - 15 ng / ml < 5 ng / ml CLPD ( corpus Luteal phase defect ) • Endometrial biopsy for histopathology examination( TB CLPD, ovulatory phase ) & invasive process. • Cervical mucus ( C.M).: Examine for spinnbarkeit test (10 cm stretching in proliferation phase . but in secretary phase cervical mucosa become tenacious and thick. it is unfavorable for sperm to pass it.

37. Hormonal level FSH,LH & prolactine levels can indicates normal or HPO axise dysfunction & or primary ovarian failure. A – high LH level in PCOD. B – High FSH level inhypothyroidism &hyperprolactenemia. C – Low estrogen level in ovarian failure D - low progesterone level in L Phase , shows CLP Dificiency. E - prolactine more than 25 ng /ml is high. schedual

38. Tubal test • HSG. • Laparoscopic chromotubation . • Sonosalpingography . • Falloscopy . • Salpingoscopy. • Insufflation test. I - HSG I - HSG thefirst important diagnostic method for evaluation of tubes. its must be done in 8 – 10 days of cycle . Action mechanism • Atropine injection to avoid tubal spasm . • Folli catheter must be use . • Wilkenson or Rubin cannules is used. • Water soluble dye better from oil media because of ( chemical peritonitis , granuloma and delayed spillage ) .

39. With HSG we can recognized • Septet uterus . • Bicornuate uterus. • Unicornuate uterus. • Asheerman syndrome. • Sub mucosal fibroid . • Patency or blockage of tubes . falls negative : Tubal spasm like block . falls positive : Hydrosalpinx like spellage . Tubercular salpingitis : it is cause extravasations of the dye and show bilateral corneal block . Complication • PID. • Allergic reaction . • Dislodgment of pregnancy. Advantages • Its a permanent record. • Its shows the site of blockage .

40. Laparoscopy Laparoscopy is indicated if : • HSG reported abnormal . • Pelvic adhesion suspected . • Endometriosis suspected . Show that • Patency of tube tested ( chromotubation ). • External adhesion of tubes. • Position of tubo ovarian fimberia. We can help these therapy processes • Adhisiolysis . • Endometriosis ablation. • Fimberioplasty . • LSC + salpingoscopy.

43. Sonosalpingography ( SSG) 100 cc serum saline + small amount of air injected transcervical in the cavity of uterus .U/S can screen the movement of the bubble & determined blockage of tube (free fluid in the Douglas pouch indicated patency of the tube in this procedure no risk of x ray & allergic reaction) Hysteroscopy falloscopy ( HF) • For uterine abnormality pathology of corneal end of fallopian tube . • Tubal polyp detection . • In this procedure we can do it cannulation & breaking of flimsy adhesions within the lumen Salpingoscopy • Visualized the fimberial & ampullary portion of the F.T laparascopically. • Peritoneal infertility causes can be detected during salpingoscopy .

44. Treatment A-Treat an ovulation • Clomephine citrate 50 mg /d from second day of the cycle . monitoring growth of F Du Graff by U/S until the follicular size reaches 20 m m .the dose may have to increased gradually up to 200mg/d in the non responders. From hyper stimulation syndrome with hCG &antiostrogenic side effect by changing over to letrozal 2.5 mg / d instead of clomephine .When follicular size reaches 20 mm , hCG 5000 iu / im give it. after 36 - 40 hour the follicular ruptured . intercourse must be arranged timely. this regime is given for 6 - 8 month .if the above regime fails following the :

45. Human menopausal gonadotrophin ( containing FSH) is given in a dose of 75 - 150 iu onward . recombination HMG is expensive but more effective . • GnRh sub cutaneous or intranasal in hypothalamic disorder Multiple pregnancy (MP)with clomephin & FSH 10 %. MP with GnRH 1 % . If failed medical therapy , donor egg or adopts with this condition .

46. POCD responds to clomephen or gonadotrophin stimulation , but hyperstimulation must be watched , if it occur hCG should be withheld in the cycle. If failed medical therapy calls for laparoscopic drilling of the cyst or cauterized. • Hyperprolactemia : Hypothyroidism & pituitary adenoma should be excluded or threaded .bromocryptine 1.25 mg TID & increased to 5 mg TID. • (CLPD) corpus luteal phase deficiency is rectified by progesterone or hCG in the leuteal phase .

47. Tubal infertility treatment • Tubal microsurgery ( tubo plasty ). • Laparoscopic T adhesiolysis and fimberioplasty . • Balloon tuboplasty and canulation through hysteroscopy ( HBT ). • IVF ( In Vetro Fertilization ). I - Tuboplasty : Excising the blocked portion & anastomosis. success depending on the sit of blockage. ( fimb 25 % , cornual end 50 % , isthemic isthmus anastomosis 60 - 70 %). Risk • Failure to restore the patency of tube. • Reblockage . • Ectopic pregnancy. two weeks after do it this procedure , needs hydrotubation also .

48. II -Laparoscopy : we can do it : • Fimberioplasty. • Adhesiolysis . • PCOD can be dealt. • Endometriosis nodules cauterization . III_ Balloon tuboplasty & cannulation . Medical end blocked by flimsy adhesion ( 40 % pregnancy occured ) IV - IVF : we don in : • Extensive Tubal damage. • Failed tuboplasty .

49. Unexplained infertility When all investigation in both male & female are normal we used this term. • Counseled on adoption. • Used newer technologies are : a - IUI ( AI ). b - IVF. c - ZIFT. d - GIFT. e - Cryopreservation technique . f - ICSI.

50. 1 – IUI or ITI Indication : • Male infertility. • Cervical mucus hostility with ab. • Unexplained infertility . Action mechanism : ovulation induction . intra uterine or fallopian insemination of washed sperms at ovulation time ( 3 - 4 cycle attempted 30 - 40 % success ).