Infertility affects as many as 10% of the couples, the causes, investigations and treatment with mention of management of fibroids and endometriosis has been done in the presentation.

1. PEARLS OF WISDOM
IN INFERTILITY
Dr. Jyoti Malik
▪ Medical Superintendent - JJ Institute of Medical Sciences, Bahadurgarh.
▪ Director, Roots IVF & Fertility Institute, JJIMS.
▪ Secretary General - Haryana Chapter of Indian Society of Assisted Reproduction
(ISAR)

2. Kanchan, 24 yrs, married for 3 yrs, now eager to conceive,
she has not used any contraception.
So when & what investigations do we advise her?

3. Is it Whenever couple feels like
having to be investigated & treated..?
• <35 Years 1 Year
>35 Years 6 Months
• >40 Years
• Oligomenorrhoea
• Amenorrhoea
• Advanced stage endometriosis
• History suggestive of ↓ ovarian reserve
• H/o previous surgeries eg salpingectomy or disease
such as Kochs abdomen etc
Immediately

5. Significance of AMH
▪ AMH < 0.3 ng/Ml – Few eggs remaining
▪ AMH levels >2.5 ng/mL - Probably normal reserve
▪ AMH > 3.6 ng/Ml – Increased risk OHSS.
▪ May reflect
fertility potential more accurately than conventional
markers like FSH, inhibin B or estradiol levels
GOOD STANDARDISED LABORATORY IS ESSENTIAL
as lab to lab variation is marked !

6. Investigations for Ovarian Reserve
• Age related decline in female fertility well recognised…
• Starts at 30
• Rapid decline after 37
• Virtually zero at 43
Ovarian Reserve Tests
1. D2 antral follicle count (<5 ,Poor outcome)
2. AMH of 2 to 6 (<1 Poor ovarian reserve, >6 PCO)
3. D2 FSH > 10 IU/l poor response to ART
No evidence for ovarian volume, ovarian blood flow, inhibin B, estradiol (E2)

7. • HSG - Screening test, cost effective,
non invasive, has high specificity &
sensitivity
• Laparoscopy - Gold standard
Final diagnostic procedure
• Routine use of diagnostic laparoscopy for
evaluation of all cases of female infertility
is currently under debate.
• It may be done:
✓ After several (usually 4) failed cycles of
ovulation induction
✓ Suspected pathology USG ??
✓ Abnormal HSG
Rt fimbrial block
? Dist hydrosalphinx
Left fimbrial block
? Distal hydrosalphinx
Bilateral Tubal Block

8. Irregular uterine outline
Bilateral tubal block
Irregular uterine
lining with filling defect
Subseptate uterus
Stenosed lower uterine segment

9. Hysteroscopy before IVF?
• Hysteroscopy in the cycle preceding a subsequent IVF attempt nearly
doubles the pregnancy rate in patients with at least two failed IVF attempts
compared with starting IVF immediately (RR = 1.7).
• This is true even in the absence of a detectable intrauterine pathology
Bosteels J. Weyers S. Puttemans P.Panayotidis C. Van Herendael B. Gomel
V.Mol BW. Mathieu C. D'Hooghe T. The effectiveness of hysteroscopy in
improving pregnancy rates in subfertile women without other gynaecological
symptoms: a systematic review. [Review] [128 refs]
Human ReproductionUpdate. 16(1):1-11, 2010 Jan-Feb

10. ▪ Detailed history
▪ Thorough clinical evaluation
▪ Lab investigations

11. Clinical Male Infertility History
Infertility History Age of partners, time attempting to conceive
Contraceptive methods/duration
Previous pregnancy (actual partner/other partner)
Sexual history Potency, libido, lubricant use
Childhood &
development
Cryptorchidism, hernia, testicular trauma, Testicular torsion, infection (eg.
Mumps orchitis), Sexual development, puberty onset
Personal history Systemic diseases (diabetes, cirrhosis, hypertension), Sexually transmitted
diseases, tuberculosis, viral infections
Previous surgeries Orchidopexy, herniorraphy, orchiectomy (testicular cancer, torsion),
Retroperitoneal and pelvic surgery, Other inguinal, scrotal and perineal
surgery
Bariatric surgery, bladder and neck surgery, transurethral resection of the
prostate
Gonadotoxin
exposure
Pesticides, alcohol, cocaine, marijuana abuse, Medication (chemotherapy
agents etc.), High temperature, Organic solvents, Heavy metals, Radiation
Family history Cystic Fibrosis, endocrine diseases, Infertility in the family
Current health
status
Respiratory infection, anosmia, Galactorrhoea, visual disturbances, Obesity

12. General
- Stature Ht ,Wt , BMI, Obesity
- TPR / BP
- Gynecomastia
- Hair distribution & amount, Subvirilization.
Genital
- Spermatic cord
- Scrotum
- Testis – mobility, consistency
- Abnormal shapes of penis, urethral meatus
Azoospermia
- Rectal exam to exclude ejaculatory duct obstruction.

13. Essential
• Detailed Semen Analysis
1. Count
2. Motility
3. Morphology
• HIV
• HBsAg
• HCV
Optional
▪ Semen culture
▪ Sperm Function Test
▪ S. FSH
▪ Testosterone
▪ Blood Sugar
▪ Colour Doppler
▪ Karyotype
▪ Y chromosome Microdeletion

14. • Cornerstone’ of lab evaluation (although it is not a sperm function
test)
• Gives information - Functional status of seminiferous tubules,
epididymides & accessory sexual glands
• Prostatic gland fluid (0.5ml - zinc, citric acid, acid phosphatase &
proteases)- assures liquefaction
• Seminal vesicle fluid (1.5-2ml -prostaglandins & fructose)
• Semen sample must be collected after min 3 days & max 7days of
abstinence.

15. Evaluation Semen Analysis
Semen volume 1.5 ml
Total sperm in the ejaculate 39 million
Sperm per ml. 15 million/ml
Vitality 58% live
Progressive motility 32 %
Total motility 40 %
Morphologically normal 4 %
• Semen analysis - In Clinical Practice, male factor infertility is identified by ABNORMAL SEMEN
PARAMETERS
• WHO (2010) guidelines for semen reporting (normal values)
• Ref - World Health Organization. NICE guideline CG156, recommendation 1.3.1.1. Oct 2014

16. Total Motile Sperm Count (TMSC)
Criteria TMSC Treatment
Pre wash TMSC > 5 million / ml IUI
Pre wash TMSC 1 - 5 million IVF
Pre wash TMSC <1 million ICSI
Hamilton JA. Total motile sperm count: a better indicator for the severity of male factor
infertility than the WHO sperm classification system. Hum Reprod .2015 May;30(5):1110-21.
10 million x 4 ml x 50 = TMC 20 million
100
Total motile sperm count = Vol. of semen sample x Total no. of sperm x
Percentage of normal motility

17. • Rinki, 30 Years old, ms 3yrs,
• MH. Reg, 28-30 days cycle
• FSH, LH, TSH : Normal
• Hsg. Bilat patent tubes
• HSA 90 mill/ml,60% active
• PLAN of Treatment : IUI

18. • D2 scan; RO CYST 32 x 28 mm, LO 7-8 AF

19. • 30 yrs old, married 5 yrs, has regular cycles
• Hormone profile is normal
• HSG shows normal uterine cavity with bilateral free spill of dye
• HSA reveals a sperm count of 20 million,40% motility, and TMC
of 8 million/ml,
• Follicular monitoring suggests ovulatory cycles.
• PLAN OF TREATMENT?

20. • Ovulation induction with Clomiphene citrate / Letrozole,
• IUI

21. • 2.5 mg once daily X 5 days (D3-7 of menstrual cycle); for 3 consecutive
cycles or till occurrence of pregnancy.
• > 3 courses of therapy not recommended.
• Dosage or duration of therapy beyond 2.5 mg/day for 5 days should
not be undertaken.

22. Female factors
Ovulatory Dysfunction
Cervical factors
Endometriosis
Immunological factors
Unexplained infertility
Male factors
Subnormal Semen
parameters;oligozoospermia,
astenozoospermia,teratozoo
spermia,hypospermia
Ejaculatory dysfunction
Retrograde ejaculation
• HIV infection

23. • Age less than 35 yrs
• Spont/induced ovulation
• At least one open fallopian tube
• Sperm count more than 10 million /ml pre wash or >5
million motile sperm with motility more than 40% post wash
• Normal uterine cavity

24. • Bilateral Tubal Block
• Severe oligoastenospermia
• Multiple infertility etiology
• Severe Endometriosis
• Older women

25. • Dr P, 35 yrs old, MS 5 yrs, has reg cycles with dysmenorrhea.
• FSH 5.3, LH 3.3 ,AMH 1.9,TSH 4.4
• Usg B/L Endometriotic cyst 27x23,37x31mm
• HSA 60 mill/ml, 48%active
• Tried Ovulation induction in 2 cycles with IUI
• IVF (after long down regulation, rec Fsh,)
• 3 oocytes /formed 2 embryos, frozen both.
• Plan embryo pooling and then FET

26. • Treatment with intra-uterine insemination (IUI)
improves fertility in minimal-mild endometriosis:
• IUI with ovarian stimulation is effective but the role of
unstimulated IUI is uncertain (Tummon et al., 1997)
For treatment of the infertility associated with mild to moderate
endometriosis, controlled ovarian hyperstimulation with intrauterine
insemination - IUI is often attempted and has a reasonable chance to
result in pregnancy “ if other infertility factors are not present”.

27. • Starting dose higher
• Early use of gonadotropins
• Role of surgery

28. SHOULD SURGERY BE PERFORMED PRIOR TO
TREATMENT WITH ART TO IMPROVE REPRODUCTIVE
OUTCOMES?
• Surgery for ovarian endometriomas may damage ovarian reserve,
potentially resulting in poor ovarian response to COH
• Removal of endometriomas was compared to non-removal by Garcia-
Velasco et al in a retrospective, matched case-control study.
“It was suggested that removal of endometriomas was associated
with lower E2 and a higher requirement of FSH as compared to non-
removal, and no differences in pregnancy rates”

29. RESPONSE OF COH IN PTS OF ENDOMETRIOSIS
(SURGICALLY CONFIRMED CASES)
• Required significantly higher dosages of gonadotropins
• Achieved lower peak E2 levels
• Yielded fewer oocytes
• Lower OHSS rate
• Higher cycle cancellation rates (Sonja Trajkovic et al, Ind J Med 2014)
• These findings suggested that the ovarian responsiveness was damaged after the
presence and excision of ovarian endometriomas.
• There are currently insufficient data to clarify whether this endometrioma related
damage to ovarian responsiveness precedes or follows surgery

30. ARGUMENTS IN FAVOR OF REMOVING
ENDOMETRIOMAS
• Endometriomas may interfere with ovarian stimulation
• Endometriomas may impose difficulties during oocyte retrieval.
• Endometriomas have been considered responsible for producing
substances that are toxic to maturing oocytes affecting cleavage after
fertilization.
• Endometriomas may themselves be responsible for compromising ovarian
reserve by destroying ovarian tissue through their expansion.

31. ARGUMENTS IN FAVOR OF NOT REMOVING
ENDOMETRIOMAS
• Endometriomas resection prior to IVF may compromise or destroy
adjacent normal ovarian tissue by removal of part of the ovarian
cortex (26- 27) or compromising ovarian artery blood flow (28)
leading to a reduced ovarian reserve.
• This is a source of concern especially in cases that a repeat
surgery is considered.
• Removal of endometriomas although classified as minimal
invasive surgery it is a procedure which can be accompanied by
life threatening complications (14).

32. AB,34 yrs, married for 5 yrs, has heavy periods and
dysmenorrhea,
Tubes show free spill on HSG
Semen parameters good.
USG revealed a heteroechoic area,4.1x3.6 cm in anterior
wall of uterus, not indenting the endometrium . Few small
3x2 cm,1.2 x1.3cm lesions also at post wall
FIBROID

33. • Fibroids affect 35-77% of reproductive age-women.
• When selecting a treatment for symptomatic fibroids, the fibroid
location, size, and number must be considered.
• Myomectomy is usually the best option for women desiring future
fertility.
• Initial fertility studies on MRgFUS and UAE are encouraging, but
RCT's need to be done.
• At this time, UAE is not recommended for women desiring to become
pregnant.

34. • Myomectomy before ART is likely to improve pregnancy outcomes in
infertile patients with submucosal fibroids, and with intramural
fibroids > 5 cm
• For subserosal fibroids, myomectomy before ART does not affect
pregnancy outcomes.
Bulletti C, DE Ziegler D, Levi Setti P, et al. Myomas, pregnancy outcome, and in vitro fertilization.
Ann N Y Acad Sci. 2004;1034:84–92. [PubMed]

35. Medication
Decrease
size/vol
Decrease
Bleeding
Side effects usage
Progestins No Yes
Fibroid proliferation off
label
OCP No Yes Minimal off label
NSAID No Yes Negligible off label
Tranexamic
acid
No Yes FDA approved

36. Medication
Decrease
size/vol
Decrease
Bleeding
Side effects
usage
GnRHa
35-65%reduct in
vol
Yes,in97% by 6
months
Estrogen
deprivation only
prep
Mifepristone
Yes,48%
reduction in vol
Yes,amenorrohea
in 60-65%
Linked with
endometriallining
SPRM
ULIPRISTAL
ACETATE
Yes 36%
Yes,90% by 10
mg dose
Linked with altered
endometrial
development
Aromatase
Inhibitors
Yes 45% No
Linked with
endometrial
stimulation

37. • Mrs AD ,23 yrs old, with BMI of 32, married for 2 yrs ,having
irregular and scanty periods, has excessive hair on chin, sides
of face, and is wanting to conceive.
• HSA is WNL
• FSH 6.7,LH 17,AMH 9.4,
• Hsg patent tubes
• USG AFC >20 RO, >18 LO
• So we r dealing a lady with PCOS

38. • Rotterdam 2003 criteria;2 out of 3 following features
1. Ovulatory dysfunction (< 21,>35 d)
2. Hyperandrogenism (clinical/biochemical)
3.PCOM on USG.
• Follicle#ovary>18& ov vol>10 ml(new technol),follicle# ov .12 or
ov vol. >10 ml (old tech)

39. • Life style (diet ,exercise) if obese.
• Ovulation induction.
• Oral agents(Letrozole,Clomiphene citrate,Metformin)
• Gonadotrophins
• Surgical (LOD)
• IVF

40. • Offer Oral Glucose Tolerance Test
• Optimize the following factors to improve reproductive &
obstetric outcomes
• Weight, diet, exercise, smoking, alcohol, BP, mental,
emotional & sexual health.

41. • Letrozole is 1st line pharmacological therapy.
• Risk of multiple pregnancies is less in comparison to CC
• Addition of Metformin to Gn for ovulation induction in IVF can
improve outcome ,and also reduce risk of OHSS
• Use Antagonist protocol for ovulation induction with agonist
trigger.Prefer rec FSH in pcos women.
• Be careful for OHSS ,and if E2 levels are high,Freeze all
embryos and transfer in next cycle.

42. Thank You