Practical Approach for Evaluation of Infertile Couple

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Practical Approach for Evaluation of Infertile Couple

Definition of Infertility


According to American Society of Reproductive Medicine (ASRM) Infertility Is defined as

  • Failure to achieve pregnancy within 12 months of unprotected intercourse
  • Failure to achieve pregnancy after therapeutic donor insemination[IUI (D)] in women younger than 35 years
  • No conceivement within six months of trial for issue in women older than 35 years.


An infertility evaluation may be offered to any patient who


a) By definition has Infertility
b) Is at high risk of infertility

 

  • Women older than 35 years should receive an expedited evaluation and undergo treatment after 6 months of failed attempts (TIC) to become pregnant or earlier.
  • Women older than 40 years more immediate evaluation and treatment are warranted.
  • If a women has a condition known to cause infertility the doctor should offer immediate evaluation.
    (ASRM)


Indications for immediate evaluation include:-

  • Oligomenorrhea or amenorrhea
  • Known or suspected uterine, tubal or peritoneal disease
  • Stage III or stage IV endometriosis
  • Known or suspected male infertility

 

Basic Infertility Evaluation


Both partner should be evaluated.


Evaluation of an infertile couple depends on thorough history and physical evaluation of the couple.

 

Who is Responsible?

We see that male and female partners both are approximately equally responsible for infertility. So Couple has to be treated together as a unit.


A very important aspect of infertility management is Counselling, Counselling and Counselling!!!. The role of counselling in the management of infertile couple cannot be underestimated, rather it is of utmost importance. Counselling at all the steps is important, starting from the first visit to each step and even at failure. The best counselor is the treating Doctor herself, but other counsellors can be hired and trained. Counsel the patient thoroughly by Audio Visual methods (Charts).


Evaluation of Infertile female - Over the period of time the evaluation of infertile couple has reduced to certain basic and concrete tests as compared to earlier long list of tests, haunting and confusing both doctor and patient. Start with a thorough History…History should be protocol based so that no aspect remains untouched


History


Duration of infertility, Menstrual history (Age at menarche, Cycle length, Severity and type of dysmenorrhea), Obstetric history (parity, previous pregnancy outcome, and associated complications), Coital frequency, Sexual dysfunction, dyspareunia, Previous methods of contraception, PID, STD, pelvic or abdominal pain, Thyroid disease, Galactorrhoea, Hirsutism, Past surgery, Results of any previous evaluation and treatment, Family history (Birth defects, mental retardation, Early menopause, Reproductive failure or compromise), Life style hazards (Exposure to known environmental hazards, History of Smoking, alcohol and drugs(SAD))


Physical Examination

  • Weight, BMI, Waist hip ratio, Blood pressure, Pulse rate.
  • Thyroid enlargement and presence of any nodules or tenderness
  • Breast Examination and evaluation for secretion, Signs of androgen excess
  • Vaginal or cervical abnormality, secretion or discharge and P/V
  • Pelvic or abdominal tenderness, organ enlargement or masses
  • Bimanual pelvic examination, Uterine size, shape, position, and mobility
  • Adnexal masses or tenderness
  • Cul-de-sac masses, tenderness, or nodularity


Obesity and Infertility has a very strong correlation, so much so that many patients conceive spontaneously after weight reduction. BMI Cut-off for Asians <18.5-underweight, 18.5-22.9-normal, 23-26.9-overweight, >=27-obese (WHO guidelines, 2010).


Investigations: Screening tests and Specific tests


Screening tests

  • CBC, ABO & RH, HPLC (Hb electrophoresis)
  • HIV 1 & 2, HBsAg, anti-HCV, VDRL
  • Diabetic profile: FBS, PPBS, RBS, HbA1C
  • OGTT, Thyroid profile (T3, T4, TSH & thyroid antibody)
  • Serum Prolactin, Liver function tests, Renal function tests
  • Rubella IgG and IgM
  • Screen for gonorrhea, chlamydia
  • Cervical smear, Urine R & M and culture sensitivity.


Specific tests

  • D2/3 hormones: FSH, LH, E2 and AMH
  • S. Testosterone, 17 OH Progesterone, Vit. D3, Lipid Profile
  • Tuberculosis profile, Chlamydial Antibody Test
  • S.CA-125, Homocysteine,
  • LAC, ACA, β2 Glycoprotein, dsDNA
  • Hereditary Thrombophilia-Anti Thrombin-III, Factor-V (Leiden),Protein-C, Protein-S, MTHFR Gene
  • Ovarian Reserve Testing (ORTs)
  • Trans-Vaginal Sonography (2D, 3D & Doppler)
  • HSG, Laparoscopy, Hysteroscopy, MRI


Three ‘MUST KNOW’ skills for ART specialist- for Doctors aspiring to take infertility management as specialty, it is mandatory to be equipped with these three basic armamentarium

  • Transvaginal Sonography
  • Laparoscopy & Hysteroscopy
  • Reproductive Endocrinology (hormones)/ ORTs


The art of learning transvaginal sonography is so much important that it is said that if you enter the field of infertility without the knowledge of this art it is almost like “walking in the dark without a torch”


Role of Ultrasound in Infertility


Trans vaginal Ultrasound, Basal D2/D3 Scan-Size and Shape of Uterus, Congenital uterine anomaly, Fibroid mapping, Adenomyosis, Preexisting cyst, Intra Uterine adhesions /synechia/ polyp


TVS & Endometrium - Endometrial thickness, Endometrial Pattern in different phases of menstrual cycle (Proliferative phase, Secretary Phase, Endomyometrial junctional zone- discrete/hazy, Endometrial Volume, 56-98% sensitivity to detect intrauterine lesion


Ultra Sound Doppler blood flow studies


Uterine and endometrial arteries resistance decreases significantly during the midluteal phase, i.e. in the period of embryo implantation (PI, less than 3.0). Endometrial blood flow evaluation is done by means of analyzing flow velocity waveforms of sub endometrial and endometrial arteries


Applebaum zones of Blood flow:


zone 1 - vessels penetrating the outer hypoechogenic area
zone 2 - vessels penetrating the hyperechogenic outer margin of the endometrium
zone 3 - vessels entering the hypoechogenic inner area of endometrium
zone 4 - up to the middle echo . Blood flow up to Zone 3 and 4 are good


USG & Ovaries- Ovarian masses, Ovarian Cyst & Endometrioma, Polycystic Ovaries, Ovarian blood flow, Antral Follicular Count (AFC) on D2/D3, Serial Folliculometry and ovulation studies-Size and number of developing follicles, Rate of follicular growth.


Folliculometry (TVS) - USG signs of ovulation, Sudden collapse of follicle, Loss of clear margins, Appearance of internal echoes in the follicle, Increase in cul-de-sac fluid volume


Ovarian Reserve Tests (ORTs)? What is ovarian Reserve? - Ovarian reserve relates to the quantity and quality of the remaining primordial follicle pool in both the ovaries at a given age. Ovarian reserve is a term that is used to determine the capacity of the ovary to provide eggs that are capable of fertilization, resulting in a healthy and successful pregnancy.


Difference between Ovarian response and ovarian reserve- Ovarian reserve may be good but ovarian response may be poor or vice versa may be true. It depends on many factors specific to the patient herself and may be due to genetic predisposition of difference in receptor responsiveness to various gonadotropins doses. So response is more important than reserve.


Ovarian reserve tests!!!


1) Age > 35 years Poor reserve
2) Basal D2/ D3 Hormones

  • FSH > 10 IU/Ml
  • AMH < 1.1 ng/ml (1.1-3.5ng/ml)
  • Estradiol (E2) < 20pg/ml & > 80pg/ml
  • Inhibin B <45pg/ml


3) Sonographic parameters

  • Antral Follicle count (AFC) <5-7
  • Ovarian volume approx. <3cc
  • Poor ovarian blood flow


4) Dynamic tests

  • Clomiphene Citrate Challenge test (CCCT)
  • Gonadotrophin Releasing Hormone agonist stimulation test (GAST)
  • Exogenous FSH Ovarian Reserve test (EFORT)


Hysterosalpingography (HSG) - HSG should be done under strict aseptic conditions by a trained person only, along with the tubal patency we can assess the Uterine cavity (septate, bicornuate, unicornuate, didelphys uterus, Endometrial Polyp, submucosal fibroid, intrauterine adhesions.


Laparoscopy- What information Laparoscopy can give? Uterus (shape, size any adhesions, Fibroids) Tubes (Architecture, Tubo-ovarian relation, Patency) Ovaries (size, Ovarian cyst, Free/Adherent) Pelvis (Endometriosis and its staging, Adhesions, Findings suggestive of tuberculosis, POD-free /obliterated).


Hysteroscopy- Gold standard for uterine cavity pathology.


Diagnostic: Uterine cavity (Normal cavity/T-shape uterine cavity, normal ostia, Polyp/submucous fibroid/adhesions, any congenital defect especially septa and its extent, Endometrial lining (strawberry type -in TB).


Therapeutic: correction of uterine malformation, septal resection, adhesiolysis, myomectomy, polypectomy, tubal cannulation.


Role of MRI in infertility- Fibroid mapping and adenomyosis, Mullerian duct anomalies and associated renal anomalies, pituitary adenoma in cases of hyper prolactinemia.


Male factor Evaluation


History- (Age, occupation, previous seminal analysis, smoking, alcohol and drug (SAD) Tobacco), Sexual history (Erectile dysfunction or ejaculatory problems, loss of libido) Medical history (Diabetes, hypertension, TB), Surgical (Hydrocele, hernia, Varicocele, Undescended testis, Appendicectomy), Family history (diabetes, hypertension, male infertility), History of consanguinity.


Physical examination - If semen analysis abnormal or sexual dysfunction

  • BMI, secondary sexual characters, Thyroid examination and arm-span.
  • Breast Examination for gynecomastia.
  • Genital Examination shape and size of penis, prepuce, position of external urethral meatus, testicular volume. (Normal 15-30 ml), palpation of epididymis and vas deferens, exclude varicocele or hydrocele.
  • Abdominal Examination for any abdominal mass, undescended testis, inguinal hernia, organomegaly or ascites.
  • Prostate enlargement by digital rectal examination (P/R).


Single most important test for male factor evaluation is good Semen Analysis (Semen Qualitative Examination -SQE) by pre and post semen processing method. SQE is different from semen analysis done in a pathology laboratory.


In an infertility centre, Semen collection is done in a clean, hygienic and separate collection room meant for the purpose.

  • Male should be abstinent for 2-7 days
  • A written protocol is provided to the male partner for semen collection.
  • Sample to be evaluated positively within half to one hour of collection (motility reduces beyond one hour)
  • Both Pre wash and Post wash sample is analysed.
  • Preferable send a semen sample for culture and sensitivity.


Commonly used semen processing techniques-Swim-Up Technique and Density Gradient Method.


Advantages of Processing Semen.

  • Improve the number of morphologically normal sperm, remove dead cells and debris.
  • Remove bacteria and other microorganisms, reduces the viral load (ideal for HIV positive patient).
  • Antibodies in seminal plasma removed, remove antigenic protein, which stimulate immune reaction in female, remove decapacitation factor.
  • Besides this, certain active substances are added by means of culture media to increase sperm motility.


Additional advanced analyses need to be carried out in case of subnormal semen parameters.

  • Endocrine evaluation : FSH, LH, testosterone, prolactin, TSH
  • Post ejaculatory urinalysis
  • Scrotal Doppler
  • Trans rectal sonography
  • Testicular biopsy/exploration
  • Genetic screening
  • Specialized sperm function tests and Sperm DNA fragmentation tests.



Infertility tests in special situations

  • Laparoscopy for unexplained infertility
  • Advanced sperm function testing(eg. DNA fragmentation testing)
  • Post coital testing
  • Thrombophilia testing
  • Immunological testing
  • Karyotype
  • Endometrial biopsy
  • Prolactin

 

Conclusion

  • 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 receive an expedited evaluation and undergo treatment after 6 month of failed attempts to become pregnant or earlier, if clinically indicated.
  • In women older than 40 years, more immediate evaluation and treatment are warranted.
  • If a women has a condition known to cause infertility, the obstetrician gynecologist should offer immediate evaluation.
  • A comprehensive medical history,including items relevant to the potential etiologies of infertility,should be obtained from the patient and partner,should one exist.
  • A targeted physical examination of the female partner should be performed with a focus on vital signs and include a thyroid, breast and pelvic examination.
  • For the female partner, tests will focus on ovarian reserve, ovulatory function, and structural abnormalities.
  • Imaging of the reproductive organs provides valuable information on conditions that affect fertility. Imaging modalities can detect tubal patency and pelvic pathology and assess ovarian reserve.
  • A women’s health specialist may reasonably obtain the male partner’s medical history and order the semen analysis. Alternatively, it is also reasonable to refer all male infertility patients to a health care specialist with expertise in male reproductive medicine.

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