Infertility

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Infertility
2

• Chairman of the Indian College of Obstetricians
  Gynecologists (ICOG)
• Past President of the Federation of Obstetric
  Gynecological Societies of India (FOGSI) 2006
• Honorary Fellow of the Royal College of
  Obstetricians Gynecologists
• Prof. and Cons. Obs. Gyn,Breach Candy
  Hospital, Jaslok Hospital,
• Sir H.N. Hospital Mumbai, India.

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Causes of Infertility

• Couples (Speroff Fritz, 2005)

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Causes of Infertility (Continued)

• Women (Speroff Fritz, 2005)

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Introduction

• Primary infertility The inability to conceive
  after 1 year of unprotected intercourse for a
  woman younger than 35, or after 6 months of
  unprotected intercourse for a woman 35 or older
  (Speroff Fritz, 2005).
• Secondary infertility The inability of a woman to
  conceive who previously was able to do so
  (Speroff Fritz, 2005).

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Unexplained Infertility
Clinical Definition Absence of a definable
cause fora couples failure to achieve pregnancy
after 12 months of attempting conception despite
a thorough evaluation Sub-fertility Any form
of reduced fertility withprolonged time of
unwantednon-conception.
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First visit

• Have both come to all visits
• Get a complete history
• Sexual history
• Educate

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Visit 1 Male History

• Past medical history
• Fathered previous pregnancies within 3 years
• Genital trauma or surgery
• Genital infections GC, Chlamydia, mumps
• Environmental heat spa, pants, sitting time
• Coital factors
• Coital frequency
• Coital technique, esp ejaculation factors

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Visit 1 Male History

• Current exposures
• Drugs b-blockers, Ca channel
• blockers,cimetidine, HMG-CoA reductase
• inhibitors
• Toxic chemicals, esp. metals and dyes
• Street drug and alcohol use
• Cigarette smoking

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Visit 1 Male Examination

• Utility is controversial
• Preferable to do exam, but little contribution
  If semen analysis is normal
• Male examination
• Masculine traits
• Varicocoele
• Hypospadias
• Urethral discharge
• Prostatitis

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Visit 1 Female History

• Prior infertility evaluation, treatments
• Hx of PID postpartum/ postTB infection
• Pelvic pain, dysmenorrhea endometriosis
• Medical diabetes, thyroid pelvic surgery
• Medications, alcohol, street drugs

Contd.
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Visit 1 Female History

• Cigarette smoking
• Galactorrhea
• Menstrual patterns
• Cycle length range (best 25-35 days apart)
• Moliminal symptoms (if present, ovulating)

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Visit 1 Female Examination

• Weight, BMI, waist circumference (PCOS)
• Skin axial hirsuitism, acne, male-pattern
  balding (PCOS)
• Breasts galactorrhea ( ?prolactin)
• Cervix mucus, friability (infection)
• Uterine corpus
• Size, shape (fibroids, uterine anomalies)
• Corpus tenderness (PID)
• Fixed retroflexion (EM)
• Adnexa tenderness (PID, EM), mass (EM, tumor)

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Visit 1 Pelvic Ultrasound

• Diagnostic pelvic ultrasound
• gt10 to 12 follicles per ovary (PCOS)
• Persistent hemorrhagic cysts with low-level
  echoes (endometriosis)
• Anatomical conditions fibroids, polyps, and
• Müllerian anomalies (uterine septum)
• Decreased ovarian volume and reduced antral
  follicle count associated with reduced fertility
• Serial TV ultrasound used to document ovulation

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Visit 1 Laboratory

• Women
• CBC, ESR
• TSH, prolactin
• Ovarian reserve testing (if indicated)
• Screen for gonorrhea, chlamydia (if indicated)
• Microscopy of cervical mucus

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Visit 1 Laboratory

• Men
• Semen analysis if has not fathered children
• Fresh sample (to lab within 30 mins.) most sperm
  in initial ejaculate
• Male should be abstinent for 48 to 72 hours

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Visit 1 Counseling

• Time intercourse just before ovulation
• Use menstrual calendar to predict ovulation
• Shortest cycle length minus 14 days
• Ovulation prediction kit to confirm ovulation

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Coital frequency and Technique

• Every other day intercourse starting 4-5 days
• before expected ovulation
• Lay supine with knees up x 20 minutes after
  intercourse
• No sperm-toxic lubricants

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Visit 1 Counseling

• Stop smoking (both partners)
• If BMI gt 30, recommend/assist with weight loss
• Preconceptional care
• Folic acid 400 mcg PO per day
• Rubella serology immunize if seronegative

Contd..
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Visit 1 Counseling

• Change medications to safer FDA pregnancy
• category
• Antihypertensives
• Anti-epileptic drugs
• Blood glucose control in diabetics

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Sperm Count

• Fresh sample (to lab within 30 mins.) most sperm
  in initial ejaculate
• Male should be abstinent for 48 to 72 hours

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Sperm Analysis

• Volume - 2.0ml or more
• pH 7.2- 8.0
• sperm concentration 20 x 10 spermatozoa/ml
  
• or
  more
• total sperm count 40 x 10 spermatozoa
  
• 
  per ejaculate or more
• motility 50 or more with
  forward
• 
  progression (categories a and b)
• or
  25 or more with ra (category a )
• 
  within 60 minutes of ejaculation

Contd.....
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Sperm Analysis

• Morphology 30 or more with normal
  forms
• Vitality 75 or more live, ie. Excluding
  dye
• White blood cells fewer that 1 x 106/ ml
• Immunobead test fewer than 20 spermatozoa
  with
• adherent
  particles
• MAR test fewer than 10
  spermatozoa with
• adherent
  particles

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Sperm Terms

• Normozoospermia
• Normal ejaculate
• Asthenozoospermia
• Teratozoospermia
• Azoospermia
• Aspermia

• Normal ejaculate
• Sperm concentration lt20 106 /ml
• lt50 spermatozoa with forward progression
• lt30 spermatozoa with normal morphology
• No spermatozoa in the ejaculate
• No ejaculate

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Tests for the lady

• Thyroid
• Midcycle progesterone level /or luteal phase
  progesterone level
• FSH/ LH
• Cortisol
• Hystersalpingogram
• Laporoscopy/hysteroscopy
• Postcoital Test

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Markers Of Ovarian Reserve

• Baseline hormones - FSH -
  Estradiol - Inhibin B -
  Antimullerian hormone
• Ultrasound parameters- Antral follicle count-
  Ovarian volume- Ovarian Stromal Blood Flow

Contd..
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Markers Of Ovarian Reserve

• Dynamic tests.- Clomiphene citrate challenge
  test (CCCT)- Exogenous FSH ovarian reserve
  test (EFFORT)- GnRH agonist stimulation test
  (GAST)

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Clomiphene Citrate Challenge Test

• Clomiphene citrate ( 100mg OD ) from D 5 to D
  9 of the cycle
• FSH measured on Day 3 and Day 10
• An abnormally high value
  ( cut off point 10 26 mIU / ml ) indicates
  diminished ovarian reserve

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Exogenous FSH Ovarian Reserve Test
( EFORT )

• Day 3 Inhibin B to be done ( Pre )
• Administer 300 IU FSH
• After 24 hrs Inhibin B to be repeated ( Post )

EFORT Values Post Inhibin B Pre Inhibin B
lt 78.6 patient is poor responder
78.6 110.4 patient is borderline gt 110.4
patient is good responder
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GnRH Agonist Stimulation Test ( GAST )

• GnRH agonist down regulation
• Administration of 100 mcg baserelin every 4 hrs
  for a total daily dose of 1200mcg
• OR
• Every 6 hrs for a total dose of 800mcg
• S FSH and S estradiol to be measured before
  and after 24 hrs of treatment
• Change in estradiol less than 180 pg/ml and / or
  FSH 9.5 IU/L predicts poor oocyte response

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Documentation of Ovulation

• Regular menstrual cycles with molimia
• Mid-luteal phase progesterone gt 9 ng/ml
• BBT
• LH surge positive ovulation prediction kit
• Pelvic ultrasound evidence of ovulation
• Secretory endometrium on endometrial biopsy

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Tests of Tubal Patency

• Hysterosalpingography
• Hydrohysterosonography
• Sonosalpingography
• Hydrogynecography or sion procedure
• Redionucleide HSG
• Selective salpingography
• Hysterosalpingographic fallopian tube
  recanalization.

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Role of Laparoscopy

• Controversial as to whether to include it in
  the basic evaluation or not
• Studies indicate that it may demonstrate
  previously undetected stage I or II
  endometriosis, periovarian or peritubal
  adhesions

Contd..
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Role of Laparoscopy

• This may alter treatment plans such as
  surgery for endometriosis or directly IVF for
  peritubal adhesion
• Can be avoided in women with a normal HSG
  in patients who may need IVF

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Laproscopy findings

• Uterus ---- fibroids
• uterine anamoly
• Tubes --- patency
• hydrosalpinx
• Ovaries --- PCOS
• chocolate cyst
• POD --- endometriosis
• adhesions

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Hysteroscopy findings

• Cervical canal --- polyps
• Uterine cavity --- adhesions
• polyps
• fibroids
• uterine anamoly
• Endometrium --- proliferative/ hyperplastic
• Tubal ostium --- visualised or not

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Post coital test

• Technique
• No longer routine, since subjective
  interpretation
• and poor correlation with pregnancy rates
• Evaluates sperm-cervical mucus interaction
• Schedule 1-3 days before expected ovulation
• Abstain x 48o, then intercourse 2-8 hrs before
  PCT
• Retrieve mucus with cytobrush or cannula

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Post coital test

• Normal findings
• Quant (4), clarity (clear) , SBK (gt8 cm), fern
  (4)
• Mucus WBC count (lt5 wbc/ HPF)
• Sperm quantity ( gt 20/ HPF correlates gt20
  million/ cc)
• Sperm motility (gt 1-3 progressively motile/ HPF)

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Fertility Treatment Goals

• To ensure patient safety
• To help a couple experience a healthy pregnancy
  and birth or an alternative way to build a family
• To use as little of a couples resources as
  necessary

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Fertility Treatment Options

• Correct ovulatory dysfunction
• Correct tubal or uterine abnormalities
• Overcome subfertile sperm parameters
• ART

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Ovulation Induction
CC GnRH HMG CCHMG/FSH
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Clomiphene Citrate
Contd...
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Letrozole
Contd...
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Tamoxifen
Inj. HCG 10,000 IU
Contd...
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CC Gonadotropins
Contd...
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Gonadotropins (Step up Regimen)
Day of cycle
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Gonadotropins (Step down Regimen)
HMG / FSH Ampoules / day
3
225 IU
150 IU
2
75 IU
1
0
10
16
2
12
14
4
6
8
Day of cycle
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GnRH Agonist Short Protocol
Inj. HCG 10,000 IU
Contd...
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GnRH Agonist Long Protocol
Contd...
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Luteal Support
Contd...
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Baseline USG
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Follicle Study
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Management of infertility in women gt30 years

• Ovarian stimulation with IUI
• Ovarian stimulation with IVF
  (own eggs)
• Ovarian stimulation with IVF
  (donor eggs)
• Surrogacy
• Adoption

For couples who do not desire medical intervention