1. The Diagnosis and Treatment of Infertility
Ashim Kumar, M.D.
Reproductive Endocrinology and Infertility
Clinical Assistant Professor,
UCLA School of Medicine
Fertility & Surgical Associates
of California,
Encino & Thousand Oaks, CA

2. Infertility 1 in 8 couples affected
Definition: Failure to conceive after 1 year of regular, unprotected intercourse
Earlier evaluation is recommended if:
Women >35 years old
Irregular menses
History of Pelvic Inflammatory Disease
Endometriosis
Men with risk factors (e.g. testicular surgery, abnormal semen analysis)

3. Female Genital Tract

4. The Menstrual Cycle
Follicular Phase
Luteal Phase

5. Fertilization & Implantation

6. Causes of Infertility ? Unusual Tubal & Pelvic Male Ovulatory
Speroff and Fritz –Clinical Gynecologic
Endocrinology and Infertility 2005

7. Critical Factors Affecting Fertility
Oocytes
Sperm
Uterus
Fallopian Tubes

8. Critical Factors Affecting Fertility
Oocytes – FSH / Estradiol
Ovarian Reserve
Age – Quality
FSH – Quantity
Ovulatory Dysfunction
Midluteal Progesterone – Ovulation
TSH & Prolactin
Sperm
Uterus
Fallopian Tubes

9. Evaluation of Ovulation
Basal BodyTemperature – Poor Sensitivity
Urinary LH kits
start 2-3 days before surge is expected
ovulation is hrs later
Midluteal Progesterone
> 3 ng/ml shows evidence of ovulation
> 10 ng/ml shows evidence of “good” ovulation
1 wk before menses is best

10. Oocyte Attrition 20 weeks in utero – 6 to 7 million Birth – 1 million
Menarche – 300,000 to 400,000
37yr – 25,000
Menopause – 1,000

11. Ovarian Reserve
is the number and quality of eggs in the ovaries

12. Quantification of Ovarian Reserve
Age
FSH
Inhibin B, AMH
Basal antral follicle count
Ovarian volume
Clomid challenge test
FSH stimulation test
Serum
U/S
Response to Stimulation

13. Age and Female Fertility
Peak fertility age 20-24
Decreases some until age 30-32
Declines rapidly after 435

14. Pregnancy rates, Live births rates and Singleton birth rates for ART-Fresh embryos
CDC Data, 2003

15. Age and Miscarriage Risk
<30 yr %
30-34 yr- 8-21%
35-39 yr %
≥40 yr %

16. Risk of Chromosomal Abnormality in Newborns by Maternal Age
Maternal Fetal Medicine: Practice and Principles.
Creasey and Resnick 1994

17. Meiotic Nondisjunction

18. Preimplantation Genetic Diagnosis

19. Preimplantation Genetic Diagnosis

20. Preimplantation Genetic Diagnosis

21. Critical Factors Affecting Fertility
Oocytes
Sperm – Semen Analysis
Volume
Concentration
Motility
Morphology
Uterus
Fallopian Tubes

22. Microscopic evaluation
Semen Analysis
The gross examination
Microscopic evaluation
Appearance (opaque)
Volume (2-6 mL)
Viscosity (liquefaction,  1 hr)
pH value (7-8)
Count ( 20 million/mL)
Motility (>50%)
Morphology ( 30 % normal)
(World Health Organization Criteria)
Other Tests
• Sperm Chromatin Structure Assay / TUNEL
• Sperm DNA Decondensation
• Sperm Penetration Tests
• Postcoital Test

23. Semen Analysis
Should be ordered in any couple who presents for infertility
Repeat if abnormal
Ideally there should be more than 10 million Normal Motile Sperm
5-20 million – insemination indicated
<1 million – ICSI indicated

24. Sperm Attrition

25. Additional Male Evaluation
FSH, LH
Testosterone
Prolactin, TSH
Karyotype
Y Chromosome Microdeletion
Urology referral – evaluation for varicocele (ultrasound)
Freeze viable sperm if undergoing a diagnostic biopsy

26. Critical Factors Affecting Fertility
Oocytes
Sperm
Uterus – HSG or SHG
Fibroids
Polyps
Synechiae
Fallopian Tubes

27. Uterine Evaluation Ultrasound Sonohysterogram (saline ultrasound)
Hysterosalpingogram
MRI
Hysteroscopy

28. Ultrasound
Evaluates uterus, adnexa and occasionally the fallopian tubes
May be helpful in diagnosing uterine abnormalities

29. Sonohystogram (SHG)
Concurrent saline distention of the uterine cavity and vaginal ultrasonography

30. Hysterosalpingogram (HSG)

31. Hysteroscopy Allows direct evaluation the uterine cavity
Concurrently diagnose and treat

32. Critical Factors Affecting Fertility
Oocytes
Sperm
Uterus
Fallopian Tubes – HSG
Patent vs. Occluded
Proximal vs. Distal Occlusion
Potential therapeutic effect

33. Hysterosalpingogram (HSG)

34. MRI In Lieu of Surgery In Preparation for Surgery
Non-surgically evaluate the uterus to differentiate between various forms of congenital anomalies
In Preparation for Surgery
To map fibroids prior to surgery
Help diagnose adenomyosis

35. Laparoscopy Allows direct visualization of the pelvic anatomy.
Can evaluate endometriosis, adhesions, uterine abnormalities or ovarian masses
Chromotubation
use of a dilute solution of blue dye instilled through the cervix
can demonstrate tubal patency or distal tubal occlusive disease.
Surgically correct the disease process

36. Laparoscopy

37. Laparoscopy
Peritubal Adhesions
Lysis of Adhesions and Chromotubation

38. Laparoscopy
Resection of Hydrosalpinx

39. Treatment - Oocytes Controlled Ovarian Hyperstimulation
Long Protocol
Antagonist
Microdose Flare
Ovulation Induction
Clomid
hMG or FSH
Clomid + FSH

40. Treatment - Sperm
Intrauterine Insemination (IUI) – place the washed sperm at the top of the uterus near the opening of the fallopian tubes
Intracytoplasmic Sperm Injection (ICSI) – directly inject each sperm into each egg

41. Treatment - Uterus
Hormonal – estrogen supplementation to increase endometrial thickness
Surgical – remove polyps, fibroids, scar tissue, septum, etc.

42. Treatment – Fallopian Tubes
Surgical – correct tubal disease, endometriosis, scar tissue
OI & IUI – if unilateral tubal obstruction
IVF – for bilateral tubal disease

43. Unexplained Infertility
Normal Semen analysis, evidence of ovulation, normal uterus, tubes are open
Surgery-Laparoscopy-to exclude endometriosis/adhesions
Consider the addition of hysteroscopy
Stepwise empiric treatment of OI & IUI and IVF

44. When to Use Assisted Reproductive Technology (ART)
Neither fallopian tube is patent
Severe endometriosis
Severe male factor infertility
Unexplained infertility
After medical treatment has failed
For genetic indications-PGD

45. Intracytoplasmic Sperm Injection (ICSI)

46. Embryo Development In Vitro
First Division
Second Division
Zygote
8-cell stage
Hatching Blastocyst
Morula
Blastocysts

47. Embryo transfer
Embryos are inserted into the uterus
Embryo

48. Preimplantation Genetic Diagnosis
a procedure that allows embryos to be tested for genetic disorders before they enter the uterus and before pregnancy has begun
Thornhill et al, JMD 2002

49. Donor Oocytes
10% of ivf cycles
Indications

50. Live Births Rates from Own vs. Donor Eggs
CDC Data, 2003

51. 2nd Opinion