APPROACH TO FEMALE INFERTILIY

1. APPROACH TO FEMALE INFERTILITY
DR. VANDANA BANSAL
MS, D.phil. (Gold Medalist), DGO, FCGP
Infertility & IVF Specialist & Advance Laparoscopic and hysteroscopic Surgeon
DIRECTOR
Arpit Test Tube Baby Centre, Prayagraj
Jeevan Jyoti Hospital, Prayagraj (U.P.)

2. The problem of infertility or sterility is as old as human evolution. A couple without a child is a
barren wedlock leading to unhappiness and frustration in life. Infertility is a public health problem
associated with medical and social consequences. Adding to the emotional and physical toll
exacted by infertility is the financial burden during extensive work-up and treatment.
Infertility is a medical condition that can cause psychological, physical, mental, spiritual, and
medical detriments to the patient.
Data indicate that ART has increase 5-10% annually
INTRODUCTION
“Human fertility is on the decline in the modern era”

3. How do we define infertility
Failure to achieve a successful pregnancy after ≥ 12 months of regular, unprotected sexual
intercourse or because of impairment of the capacity to reproduce either as an individual or
with a partner.
 Under 35 year :No conception after one year of unprotected intercourse
 Over 35 year :No conception after 6 months of unprotected intercourse
Sub-fertility, Involuntary infertility
1. Primary infertility
- a couple that has never conceived.
2. Secondary infertility
- infertility that occurs after previous pregnancy regardless of outcome
Fifteen studies supplied estimates of primary and secondary infertility occurrence in 6400 infertile
couple. Out of 6400 infertile patients 3600 (56.25%) imparting with number one and 2800 (43.2%)
imparting with secondary infertility.
INFERTILITY

4. Why we are worried?
Factors in Male & Female both 15%
Unexplained 10 to 15%
Worldwide 60-80 million couple have infertility
For couple in 30-35 age group, it is 1 in 7 couple.
For couple in 35-40 age group, it is 1 in 5 couple.
For couple in 40-45 age group, it is 1 in 4 couple.
Worldwide, infertility rates are higher in Eastern Europe,
North Africa, and the Middle East. Worldwide,2% of women aged 20 to 44 were never able to
have a live birth, and 11% with a previous live birth were unable to have an additional birth
BURDEN OF INFERTILITY

5. Is infertility on rise?
• Late marriage
• Delay child bearing
• Rise in live in relationship
• Stressful lifestyle- environmental toxins, Radiation
• Obesity
• High junk food intake
• Smoking
• Alcohol
• Drug-addiction

6. How does Age affects a woman's
ability to have children?
Age of women is very important factor in deciding modality of infertility.
treatment
Primitive germ cells provide 1 to 2 million oocytes in the ovaries at birth
At puberty, this number is reduced through cell death to approximately 300,000
With increasing age quality and quantity of oocytes decrease
Aging oocytes leads to
↓ Pregnancy rate
↑ Miscarriage rate
↑ Risk of chromosomal problems, like Down’s syndrome
↑ Obstetrical complications like PIH and Diabetes
Fertility declines after 30 years, further after 35 years and grossly after 40 years
Decreased in oocyte quantity
Enhanced follicular atresia
Increased rate of chromosomal abnormalities.

7. • Ovulatory disorders - 25%
• Endometriosis - 15%
• Pelvic adhesions - 12%
• Tubal blockage - 11%
• Other tubal/uterine abnormalities - 11%
• Hyperprolactinemia - 7%
In a study of 8500 infertile couples done by the World
Health Organization (WHO) The most common identifiable
female factors which accounted for 81 percent of female
infertility, included:
CAUSES OF FEMALE INFERTILITY

8. Pelvic factors
1.Congenital malformation of the reproductive system,
- Müllerian duct aplasia
2. Cervical factors,
-Anatomical, Cervical Tear,
- cervical insufficiency & diseases, Erosion, Polyp
- Anti-sperm antibodies.
3. Uterine disorder
- endometrial lesions,( tuberculous endometritis, polyps etc)
- uterine tumors,(fibroids), Adenomyosis
- Endometrium-thin, hyperplastic
- intrauterine adhesions(Asherman’s syndrome,)
4. Oviduct and its surrounding disorders,
- oviduct obstruction,
- peritubal adhesions,
- hydrosalpinx, and
- pelvic adhesion
5. Endometriosis.
Tubal factors
Congenital absence of both tubes
Bilateral tubal obstruction causing endosalpingitis
or perisalpingitis.
• PID : Genital Tuberculosis, Post gonococcal,
Pyogenic infection
• Pelvic endometriosis
• Post operative adhesions producing bilateral
obstructions.
• Tubectomy
Vaginal Causes of Infertility
• Imperforate hymen
• Blockage of the vagina
• Extremely narrow vagina
• Painful infections in the vagina
• Vaginismus
• Immunological
CAUSES OF FEMALE INFERTILITY

9. World Health Organization subdivided ovulatory disorders into four classes:
1. Hypogonadotropic hypogonadal anovulation: i.e., hypothalamic
amenorrhea
2. Normogonadotropic normoestrogenic anovulation: i.e., polycystic
ovarian syndrome (PCOS)
3. Hypergonadotropic hypoestrogenic anovulation: i.e., premature
ovarian failure
4. Hyperprolactinemic anovulation: i.e., pituitary adenoma
Ovulatory dysfunction (defined as a history of oligomenorrhea or amenorrhea or as luteal progesterone levels
repeatedly less than 3 ng/mL, or both) accounts for a significant proportion of female infertility
OVULATORY DYSFUNCTION

10. Evaluation of Infertile Couple
• Both partner should be seen evaluated and treated Simultaneously
• Couple evaluation has positive phycological benefits
• The protocol vary from country to country and institution to institution
• Based on the history and clinical examination the next diagnostic evaluation should be carried
out in a systematically which should also be cost effective to come to definite cause of infertility.
• The endpoint should be shifted from conception to live birth.

11. The American College of Obstetricians and Gynecologists (ACOG) and the American Society for Reproductive Medicine (ASRM) make
the following recommendations.
An infertility evaluation may be offered to any patient who by definition has infertility or is at high risk of infertility.
• Women older than 35 years should be evaluated and undergo treatment after 6 months of failure to conceive
or earlier.
• women older than 40 years, immediate evaluation and treatment warranted.
• If a woman has a condition known to cause infertility, immediate evaluation.
• Comprehensive medical history ,including relevant to the potential etiologies of infertility .should be obtained
from both partner,
• Targeted physical examination of the female partner with a focus on vital signs
• Including a thyroid, breast, and pelvic examination.
• Focus on evaluation of ovarian reserve, ovulatory function, and structural abnormalities
• Imaging modalities to detect tubal patency and pelvic pathology and assess ovarian reserve.
To obtain the male partner’s medical history and evaluate semen analysis parameter or refer male infertility
patients to expert specialist in male reproductive
EVALUATION

12. Indications for earlier or immediate evaluation include the following:
• Oligomenorrhea or amenorrhea
• Known or suspected uterine, tubal, or peritoneal
disease
• Stage III or stage IV endometriosis and
• Known or suspected male infertility
• Women over 35 Year

13. • History
• Physical
• Prepregnancy evaluation
• Additional evaluation for etiology of infertility
• Diminished ovarian reserve
- Antimullerian hormone or basal follicle-stimulating hormone plus estradiol
-Transvaginal ultrasonography with antral follicle count
• Ovulatory dysfunction
- Ovulatory function test (eg, serum progesterone measurement)
• Tubal factor
- Hysterosalpingography
- Hysterosalpingo-contrast sonography
• Uterine factor
- Transvaginal ultrasonography
- Sonohysterography
- Hysteroscopy
- Hysterosalpingography
APPROCH TO FEMALE EVALUATION

14. • Whether the reproductive-aged patient is currently using contraception or planning pregnancy.
• Prepregnancy counseling should occur several times during a woman's reproductive lifespan,
because health status and risk factors can change over time maximizing her reproductive and
pregnancy outcomes.
• Chronic medical conditions such as diabetes, hypertension, psychiatric illness, and thyroid disease
have implications for pregnancy outcomes and should be optimally managed before pregnancy.
Recommendations for screening-
 Sexually transmitted infection
 Screening for the same genetic conditions as recommended for pregnant women.
 All patients should be routinely asked about their use of alcohol, nicotine products, and drugs,
including prescription opioids and other medications used for nonmedical reasons.
 Female Prepregnancy folic acid supplementation should be encouraged to reduce the risk of neural
tube defects.
 Role of micro-nutrient & Diet
PREPREGNANCY EVALUATION

15. • Duration of infertility
- Past treatment history
- Menstrual history
• Previous any pregnancy history
- Past contraception use
- History of sexual dysfunction
• Previous surgical history
- Hospitalizations history
- Pelvic inflammatory disease
- Medical history like thyroid disease, galactorrhea, and hirsutism
• History of abnormal Pap smears
- Family history of congenital defect
• History of occupation
- addiction to any substances
RELEVANT HISTORY

16. Examination of Female partner
General Examination :
• Presence of features of syndromes : Turner’s syndrome, Cushing’s syndrome.
• Second sexual characters: Hirsutism, Presence of acne
• Severe pallor
• Breasts for galactorrhea, thyroid
• Signs of tuberculosis : scars, sinuses
Local examination: Perform per speculum & per vaginal examinations for any obvious abnormalities.
• Imperforate or rigid hymen, Vaginismus
• Malformation-aplasia or hypoplasia of uterus
• Aplasia of vagina, trasverse vaginal septum
• Adnexal masses (PCOS, pelvic inflammatory disease masses: tubercular, gonococcal; ovarian
tumors)
• Uterine enlargement multiple leiomyomas
• Signs suggestive of pelvic endometriosis (uterosacral nodularity)
Examination Under Transvaginal Sonography (TVS): To compliment and confirm

17. Counselling of infertile couple
• Couple’s interview is conducted together as well as separately
• Psychological counselling - at various levels
• Counselling by trained personnel.
• Scoring system : A B C
• Preparation for the procedure
• Clinical counselling
• Discuss diagnosis,
• Plan of treatment with duration,
• Treatment options,
• Success rate of procedure.
• OPD
• Procedure:
• Pre-procedure, Procedure, Post-procedure - Related Counselling & Consent
• Documentation:
• Written, Video, Special cases separate consent - on stamp paper & can be notarized

18. Evaluation of Male Partner
• General physical examination and medical history
• Semen analysis.
• Scrotal ultrasound
• Hormone testing
• Post-ejaculation urinalysis( to rule out retrograde ejaculation).
• Genetic tests
• Testicular biopsy.
• Specialized sperm function tests

19. Preliminary fertility investigations
Day 2-4 follicle-stimulating hormone, luteinising hormone, oestradiol
Anti-Mullerian hormone
Thyroid stimulating hormone
Transvaginal ultrasonography of the pelvis: antral follicle count, pelvic anatomy
and features of deep infiltrating endometriosis
Blood group and antibody screen
Full blood examination
Rubella, varicella immunoglobulin G
Hepatitis B, hepatitis C, human immunodeficiency virus and syphilis serology
Genetic carrier screening if desired: thalassaemia, triple screen (fragile X
syndrome, cystic fibrosis, spinal muscular atrophy), extended carrier screen

20. Transvaginal ultrasonography
•Baseline scan- done in day 2 or day 3 of menstrual cycle.
It Measure the Ovarian size and volume,Ovarian Position, any cyst / pathology of Adnexa, Antral follicle
count(Low antral follicle count may be defined as fewer than 5–7 follicles,
With poor response to ovarian stimulation,
AFC may be elevated in women with polycystic ovary syndrome(PCOS))
•Preovulatory scan- Day 9 or 10 of natural or IUI cycle, Day 5 or 6 of IVF cycle and serial scan
•Luteal phase scan- Assessment of the Rupture of follicle, establish the presence of an adequately functioning
corpus luteum, luteal blood flow in Color Doppler with R.I 0.35-0.50 and PSV10-15.
•TVS is also a very good predictor for the prediction of different physiological changes undergoing at the level of
endometrium during pre-ovulatory and luteal phase of the cycle
• 3D USG
Ovulation Induction is monitored to Identify Ovarian response in natural cycle, IUI cycle and IVF Cycle.
MATURE DOMINANT FOLLICLE IN 2D AND
COLOR DOPLER
•In stimulated cycles (IUI / IVF) it helps check if
the ovulation stimulation is optimum, whether the
parameters suggest a cycle to be cancelled, and
also decide the timing for trigger.

21. • Basal body temperature
• Cervical mucus study: Fern test
• Spinnbarkeit test
• Vaginal cytology
• Endometrial biopsy
• Midluteal S progesterone A concentration greater than 3.0 ng/mL in a blood sample drawn between days 19 and
23 is consistent with ovulation, whereas a concentration greater than 10 ng/mL implies adequate luteal support.
• ovulation predictor Kits (Detect LH Surge)- detects a rise in luteinizing hormone (LH) in the urine, begin testing 3
to 5 days prior to the expected date of ovulation. positive result means that ovulation will be in the next 24 to 36
hours.
• Ultrasonography- TVS & Color Doppler.
OVULATION PREDICTORS

22. INVESTIGATIONS
LAB INVESTIGATIONS DIAGNOSTIC APPROACH
EVALUATION
OVULATORY
Evaluation of peripheral or end-organ changes
• Basal Body Temperature
• Cervical mucus study
• Vaginal cytology
• Hormone estimation
- Serum progesterone — Serum LH
- Urine LH
- Serum estradiol
- Endometrial biopsy
History, Physical examination and basic investigation
ANOVULATORY CYCLES
Endocrine
evaluation
(FSH, LH, DHEA-S
TSH, Prolactin)
TUBAL AND UTERINE FACTORS CERVICAL FACTORS
Postcoital test for
immunological factor
Endometrial
biopsy
Hysterosalpingography
Hystero-salpingo-
contrast sonography
Laparoscopy and dye
hydrotubation test and
hysteroscopy

23. Anovulatory cycles
Endocrine evaluation
(FSH, LH, DHEA-S
TSH, Prolactin)
DHEA-S LH, FSH, AMH FSH, LH LH, FSH TSH Prolactin
Adrenal
disease
Polycystic
Ovarian
syndrome
Premature ovarian
failure or resistant
Ovarian syndrome
Hypogonadotropic
hypogonadism
Hypothyroidism Prolactinoma
Testosterone,
DHEA-S,
17-Hydroxyprogesterone

24. Ovarian Reserve Testing
ovarian reserve, represents the number of oocytes available for potential fertilization at that point in time and may
be assessed by serum tests or ultrasonography.
1. Age
2. AMH
3. AFC
Day #3 FSH (<10 mIU/ml) and estradiol (<80 pg/ml)
-Correlates with the functional status of the ovaries and the quality of the oocytes
- FSH >15 only 5% success with IVF
- High estradiol level increases risk of cancelling IVF cycle
Ovarian reserve tests are good predictors of response to ovarian stimulation, but poor results do not
necessarily predict inability to achieve a live birth.

25. Diminished Ovarian Reserve
The presence of decreased ovarian reserve predicts future response to ovarian stimulation
Although there are no definitive criteria for diminished ovarian reserve, the following values may
be considered consistent with diminished ovarian reserve:
• Antimullerian hormone (AMH) value less than 1 ng/mL
• antral follicle count less than 5–7 and
• follicle-stimulating hormone (FSH) greater than 10 IU/L
or
• a history of poor response to in vitro fertilization
stimulation (fewer than four oocytes at time of egg
retrieval).

26. Most common type of Normogonadotropic normoestrogenic anovulation is PCOS.
• PCOS accounts for 80 to 85%
• 8% of all reproductive-aged females.
• PCOS can be diagnosed using the.
Rotterdam criteria for PCOS, which requires at least two of the three below listed criteria in the absence
of other pathological causes.
• Oligoovulation/anovulation
• Clinical signs of hyperandrogenism and/or serological elevations of androgens
• Polycystic ovaries demonstrated with ultrasound
• PCOS is a diagnosis of exclusion
PCOD

27. Hysterosalpingography (HSG)
Chlamydia Antibody Test
Assesses shape of the uterine cavity-Evaluates Tubal
Less invasive and cost effective
Assessment of tubal abnormalities
- Tubal occlusion
- Tubal irregularity
- Peritubal Abnormalities
HSG: Hydrosalpinx
HSG: Unilateral
Blocked Tube
Arcuate uterus Intrauterine adhesions
• Tubal spasm
• Only 38% tubal blockage is confirm by laparoscopy
• More specific for detecting distal tubal occlusion
• Diagnostic And Therapeutic specially with oil
based media.
The positive predictive value and negative predictive value of HSG for assessing tubal patency have been
estimated as 38% and 94%, respectively
TUBAL EVALUATION

28. Sonohysterography is the visualization of the uterus and adnexa ultrasonographically with the infusion of fluid
through a transcervical catheter
Using sonohysterography, the uterine cavity usually is easily defined, and abnormalities such as endometrial
polyps, submucosal fibroids, and intrauterine adhesions can be seen. More than 16% of infertile women and
40% of women with abnormal uterine bleeding will have an abnormality on sonohysterography .
Sonohysterography has a sensitivity and specificity of 91% and 84%, respectively, for the detection of
intrauterine structures
HyCoSy (hysterosalpingo contrast sonography)
- with automated 3D-coded contrast imaging technology.
Laparoscopy with chromopertubation
Tubal evaluation Hysterosalpingo-contrast
sonography (HyCoSy)

29. Other Tests
 Hysteroscopic evaluation
 To evaluate condition of uterine
 Cavity (polyps, fibroids(sub-mucus), intra cavitary lesion, intra uterine
adhesion( uterine synechiae), Mullerian duct anomalies(uterine septum)
Endometritis
 Laparoscopic evaluation
 Although considered as gold standard not taken as routine investigation
these days.
 Check patency of fallopian tubes specially in unexplained infertility .
 Tubal adhesions
 To evaluate for pelvic disease,
 Endometriosis (grading & Treatment)
 Ovarian Pathology or uterine fibroid distorting cavity.
 Mullerian anomalies

30. INDICATION OF MRI IN FEMALE INFERTILITY
• Complex adnexal masses
• Endometriosis deep seated
• Mullerian duct anomalies
• Adenomyosis
• Fibroids- Pre surgical mapping of location and vascularity of fibroid.
• Intra uterine adhesion
• Pyosalpinx
• Cornual fibroid
MRI is superior to USG in determining both tubal and peritubal component of PID.
In the era of evidence based medicine. MRI has on indispensable role in diagnosis & management of female
infertility
Non-invasive radiation free modality

31. • Laparoscopy for unexplained infertility
• Advanced sperm function testing (eg, DNA fragmentation
testing)
• Postcoital testing
• Thrombophilia testing
• Immunologic testing
• Karyotype
• Endometrial biopsy
• Prolactin
Infertility test that should not be routinely ordered

32. Unexplained infertility may be diagnosed in as many as 19-20% of infertile couples the basic infertility
evaluation is performed, and all the tests results are normal. At a minimum, these patients have
evidence of ovulation, tubal patency, and a normal semen analysis
UNEXPLAINED INFERTILITY
• For most couples with unexplained infertility, the best initial therapy is a course (typically 3 or 4
cycles) of OS and IUI, either with clomiphene or letrozole, followed by IVF for those couples
unsuccessful in achieving a pregnancy with OS and IUI.
• There is a pressing need for additional therapies to bridge the wide gap in effectiveness between
OS and IUI with oral medications and IVF.
• Further research is needed into methods to improve access to care, including ART treatments.

33. Environmental toxins affecting fertility
• Pesticides
• Mercury
• Lead
• Cadmium
• Bisphenol- A
• Flame retardance
• Phthalates

34. • Age
• Duration of infertility
• Cause of infertility
• Financial resources
• Sperm concentration in the sample
In treatment main deciding factor are:
Factors affecting modality of
infertility treatment

35. Lifestyle Changes
The ideal BMI for getting pregnant is between 18.5 and 24.9.
Diet and Exercise
• Women with extremes in body mass index (BMI) frequently present with infertility and ovulatory dysfunction.
• Women with a BMI of less than 17 kg/m^2 with a history of intense exercise regimens or women with eating
disorders are likely to develop hypogonadotropic hypogonadism, which causes deceased pituitary
gonadotropin secretions
• Women with a BMI greater than 27 kg/m^2 with anovulation can improve ovulation with weight loss alone.
Multiple studies have shown that a loss of 10% of body weight will restore normal ovulation in 50 to 100% of
women in less than 1 year .
• Bariatric surgery
Treatment / Management

36. Infertility Period
APPROACH TO TREATMENT ALGORITHM

37. APPROACH TO TREATMENT ALGORITHM
Age Factor

38. Treatment options… Overcoming
Infertility
Nearly 90% of all infertility cases, both male and female factor, all can
be treated .
Treatment options are:
• Expectant Treatment
• Ovulation Induction & COH
• Medical & Surgical treatment of Male
• Laparoscopic & Hysteroscopic Surgery for Female
• Intrauterine Insemination (IUI)

39. When to attempt IUI First
• At least one unblocked fallopian tube
• Able to ovulate, perhaps with the help of fertility medications
• Healthy ovarian reserve, good amount of healthy eggs
• Normal uterine cavity
• Cervical issue scarring/hostile cervix may block fertilization
• Mild ovulation issue like polycystic ovarian syndrome (PCOS)
• Donor sperm
• Mild to moderate male factor
• After male fertility preservation before cancer treatment or surgery
• Same sex couple

40. Intra-Uterine Insemination (IUI)
• First line of treatment provided both or either one fallopian tubes are
patent. specially in pt under age of 35 years
• Simple, Non-Invasive & Cost Effective
• IUI is a viable option before proceeding to ART
• Processed total motile sperm(PTMS)>1 million/ml
• Progressive motility >30%, morphology >4%, is the most important
criteria. Sperm survival <70%
• Prewash IUI semen pregnancy score (IUI-SPS)<150
• IUI+ mild COH- gives good pregnancy rate
• Clinical pregnancy rate per cycle is 10-20%

41. 8 Tips for fertility wellness
• Decrees stress
• Solid 8 hours of sleep
• Practice mindful eating
• Cultivate supportive network
• Balance being and doing fertile window
• Regular Exercise but not excessive
• Treat each day as new opportunity
• Meditation (Can be done with brahma Kumari)

42. Timely Referral To Specialist Care

43. Summary
• There are potential consequences of delayed, later-age referral to a reproductive endocrinology and
infertility (REI) specialist
• Diagnostic tests are conducted after
- 1 year of infertility for woman aged <35 years
- 6 months of infertility for woman aged > 35 years
• The Ob/Gy fertility specialist and patient need to work together to determine reasonable expectations and
optimal treatment course
• Due to new ART laws early child bearing should be promoted and fertility preservation by egg freezing
should be done in case of delayed marriage and child bearing.
• Diagnostic laparoscopy is no more a routine investigation for tubal testing.
• Role of color doppler and 3D ultrasound is promising.
• Role of MRI in fibroid, complex ovarium masses and PID is increasing.
• The endpoint should be shifted from conception to live birth.
• Evaluation should be done systematically which should also be cost effective to come to definite cause of
infertility. 43