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Subfertility

Ms Ann, a 21-year-old lady attends the fertility clinic with


her husband. She has been married for 2 years and not been
able to conceive despite regular unprotected coitus. A week
ago the couple had gone for evaluation to their GP and he
has referred the couple to you for further management. She
has visited her GP before for her menstrual problems. She
also had occasional vaginal discharge for which she was
treated vaginal pessaries.
DEFINITION
Subfertility is defined as inability to conceive
after having regular unprotected sexual
intercourse ( 2-3 times a week) after 1 year.
PRIMARY AND SECONDARY SUBFERTILITY

Primary-couple has never conceived before.

Secondary-the couple conceived before and


the outcome of the pregnancy was either
miscarriage , still birth or full term
pregnancy following which she is unable to
conceive.
MALE FACTORS

3 categories:
1. Sperm production
2. Sperm transport
3. Sperm deposition
SPERM PRODUCTION
Lack of production of sperms mainly due to damaged
testis or destruction of it after production.
Therefore not enough sperm to achieve fertilisation in
natural way.

1.Inadequate sperm production:


Maldevelopment of testis
Faulty descent of testis
Viral orchitis due to mumps in childhood
2. Sperm rapidly destroyed after production
Testicular damage due to x-ray or trauma
Exposure of testes to heat by tight
undergarment
Diseases like Tuberculosis,Diabetes Mellitus
SPERM TRANSPORT
The sperm production is normal but there is obstruction somewhere in
the ductal system which allows the passage of sperms out of the testis
to the penis.
Obstruction in sperm transport:
Damage to the duct system by trauma
Herniorrhaphy injuring the
spermatic cord
Tuberculous epididymis
Absence of vas deferens(congenital)
Congenital obstruction of epididymis
SPERM DEPOSITION
 The sperm production and duct system is normal but there is
faulty ejaculatory process by which sperms not deposited into the
vagina.
Ejaculatory problems:
 Erectile dysfunction
 Premature ejaculation
 Retrograde ejaculation
 Drugs like (Tricyclic antidepressants)-
affect pituitary axis,decreased libido
and erectile dysfunction.
FEMALE FACTORS

2 categories:
1. Anovulatory/oligo-ovulation
2. Anatomical and
tubo-peritoneal dysfunction
ANOVULATORY/OLIGO-OVULATION
Anovulation : no ovulation
Oligo-ovulation : infrequent or irregular ovulation

Arises due to defects in the hypothalamus, the pituitary or the ovary.

Causes are:
1.Polycystic ovarian syndrome(PCOS)-most common cause
2.Hyperprolactinemia-seen in prolactinoma
3.Hypothyroidism
4.Premature ovarian failure-total failure of ovaries in women under
the age of 40 years
5.Luteal phase defect
ANATOMICAL &
TUBO-PERITONEAL DYSFUNCTION
 Major reason for causing infertility
 The causes are as follows:
1. Uterine factors-congenital/acquired
2. Cervical factors-cervical stenosis, anti sperm Ab
3. Vaginal factors-vaginal infection
4. Endometriosis
5. Salpingitis(PID)-lead to impaired oocyte picked-
up mechanism or to damaged tubal epithelium.
Cervical stenosis
DISORDER OF IMPLANTATION

Defectsrelated to endometrial
development and maintenance.

Submucous Fibroids - benign tumour


Found in the muscular wall of the
uterus distorting the endometrial cavity.
ASSESSMENT OF INFERTILE COUPLE

History taking obtained from both the partners


Age , occupations
Frequency (timing of coitus & dyspareunia).
Lifestyle pattern-use of Alcohol, smoking, and recreational
drugs?
STDs (Past or Present)
Assessed for anxiety and stress factors
Past medical and surgical history
Specific History Questions

Female Male
 Gynecological History • History of sexual
- menstrual history dysfunction (Erectile
- last menstrual period dysfunction/ premature
 Previous pregnancies ejaculation)
(miscarriage, still birth)
• History of mumps or
 Contraception history
measles infection
 Past histroy of infection ( STD/ PID)
 Other problems: • History of lump in scrotal
- Post-coital bleeding area/ surgery to testis
- Symptoms of PCOS
- Thyroid Disorder(hypothyroidism)
- Hyperprolactinaemia(oligomenorrhea,
galactorrhea, acne)
Examination
 For male:
 Look any abnormalities of penis , testicular location , scrotal abnormality

 For female:
 Obesity(calculated by BMI)
 Examination of breast-look for galactorrhea
 Look for thyroid enlargement
 Abdominal examination-Rule out any mass per abdomen like leiomyoma or
chocolate cysts.
 Speculum examination-look any vaginal discharge.
 Bimanual examination -look for retroverted uterus & mobility of uterus
 Cervical motion-suggestive of endometriosis/pelvic inflammatory
disease(PID).
INVESTIGATION FOR FEMALE

Transvaginalultrasound: To assess the normal


anatomy of uterus, ovaries & endometrial thickness.

Hormonal evaluation: depending on regularity of


menstrual cycle. Detailed endocrinological profile if
the menstrual cycle is irregular.
Hormone Normal level Comment

Follicular stimulating hormone 4 - 20 mIU/ml Low FSH level is seen if the


(FSH) woman is not ovulating

Luteinising hormone (LH) 5 to 25 IU/L High LH level is seen if the


woman is not ovulating, in ovarian
hypofunction (produce little no or
hormones)

Prolactin 2 - 29 ng/mL (non-pregnant)

Thyroid stimulating hormone 0.4 - 4.0mIU/L


(TSH)
T4 4.5 to 11.2 mcg/dL

Free Testosterone levels 1.0–8.5 pg/mL (3.5–29.5 pmol/L) Levels are most often checked to
evaluate signs of higher
testosterone levels (Irregular or
absent menstrual periods, male
type baldness, change in voice)
Tubal Patency Test:
 Hysterosalpingogram (HSG)
Itis non-invasive outpatient procedure done in radiology.
Injected radio-opaque contrast into cervix by Leech-Wilkinson’s
canula or Foley’s catheter.

Under fluoroscopy:
Filling of the uterine cavity with the contrast
Any spillage of the dye into peritoneal cavity.
-normal uterine cavity will be triangular
Detect abnormalities in the uterus, such as an
abnormal shape or structure, an injury, polyps, fibroids,
adhesions, or a foreign object in the uterus.

Normal HSG Blocked fallopian tube


 Laparoscopic Dye Testing:
Similar to HSG but done under anaesthesia.
 Chromotubation-infusion of dye transcervically gives
information on tubal patency.
 Able to detect advanced endometriosis (early disease
peritoneal biopsy is indicated)
Laparoscopy showing normal uterus, Laparoscopy showing hydrosalpinx
ovaries and fallopian tubes
http://www.ivf-
infertility.com/infertility/investigations/female/laparoscopy.php
Dye seen spilling from the Fallopian tube Laparoscopy showing pelvic adhesions

http://www.ivf-
infertility.com/infertility/investigations/female/laparoscopy.php
Laparoscopy showing perihepatic adhesions Laparoscopy showing bicornuate uterus

http://www.ivf-
infertility.com/infertility/investigations/female/laparoscopy.php
 Advantages of laparoscopy and dye testing over
HSG
◦ The surrounding pathology in the peritubal region can
be visualised. (e.g: adhesions or endometriotic deposits.)
◦ Treatment of the above conditions can be done in the
same procedure by adhesiolysis and cauterisation of the
endometriotic deposits.

Diagnostic laparoscopy is considered as the gold standard for


evaluation of pelvic pathology. However, one drawback is
that this method cannot detect the exact site of the
blockage in the tube.
INVESTIGATION FOR MALE
 Semen analysis
A sample of the male partner’s semen is collected in a clean wide
mouthed container obtained by masturbation with minimum of 3
days of abstinence.
The sample is then checked under microscope for determination of
various normal parameters of semen shown below.
Parameters Minimum value
Total volume 1.5 ml
Total sperm per ejaculate 39 million
Sperm per ml 15 million/ml
Progressive motility 32%
Total motility 40%
Morphologically normal 4%
Normal semen analysis report (WHO 2010)
 Abnormalities of semen analysis
 Aspermia: absence of semen
 Azoospermia: absence of sperm
 Hypospermia: low semen volume
 Oligozoospermia: low sperm count
 Asthenozoospermia: poor sperm motility
 Teratozoospermia: sperm carry more morphological
defects than usual.
Testicular biopsy

 Done when semen analysis shows azoospermia. It helps


in differentiating an obstructive pathology and a
testicular pathology.
 If mature or immature sperms are present in the sample,
then these patients may suffer from a blockage of the
epididymal duct.
 If there are no sperm seen in the sample, the pathology
is usually testicular in origin.
MANAGEMENT
1. Medical
2. Surgical
3. Assisted Reproductive techniques
Counselling
 Is an essential part of subfertility management.
 Men with sperm abnormalities tend to suffer low self-esteem
while women often blame themselves with 5% having suicidal
tendencies.
 Both of the couple addressing their
concerns and social issues
MALE INFERTILITY

Medical :
 Lifestyle modification
– quit smoking and alcohol
- Wear loose undergarments
 Antioxidant (ie: Coenzyme Q10) if there is only
asthenozoospermia
 Low dose clomiphene citrate for 3 months (if semen analysis is
abnormal-count, morphology and motility)
 Sildenafil citrate in case of erectile dysfunction
Surgical
 Only done when a blockage has been detected by
testicular biopsy( to correct blockage)
 Varicocelectomy done in men with varicocele to
improve sperm count
FEMALE INFERTILITY
Lifestyle modification
 Weight loss in obese women
 Stress management

Medical (for women with ovulation dysfunction)


1. Clomiphene citrate
 50mg from day 2 of the cycle for 5 days
 Not exceeding 150mg as it will cause ovarian hyperstimulation
syndrome (OHSS)
 Long term use is associated with epithelial ovarian cancer
(hence do not use more than 6 cycles)
2. Gonadotrophin
 Human Menopausal Gonadotrophin (hMG) and
recombinant FSH
 More effective for ovulation induction however
predispose the women to higher chance of OHSS
 Balance has to be maintained

3. Metformin
 Facilitating ovulation induction in obese PCOS
 Acts as insulin sensitizer-reduce insulin
resistance(which is thought to cause PCOS)
 Metformin helps prevent miscarriage in PCOS
Surgery
 Limited
 Laparoscopic cauterization of endometriotic deposits and chocolate

cystectomy improves ovulation process.


 Adhesiolysis is indicated in pelvic adhesive disease due to PID and

endometriosis.

 Ovarian drilling in women with PCOS resistant to clomiphene therapy


for inducing ovulation. This treatment results in a dramatic lowering of
male hormones within days

 Hysteroscopic resection of submucous fibroids for better implantation


and pregnancy rates
 Myomectomy indicated in infertile women with leiomyoma ( if fibroids

located intramurally or submucously)


Assisted Reproductive Techniques (ART)
 The commonly used techniques of intrauterine
insemination, IVF (In vitro fertilisation) and ICSI
(intracytoplasmic sperm injection) are widely used
throughout the world.

Rely on basic concept of placing


the egg and sperm in close proximity
to facilitate fertilisation.
 Intrauterine insemination- with or without stimulation with
FSH
◦ Unexplained subfertility, Anovulation unresponsive to
ovulation induction(OI), Minimal to mild endometriosis
 Donor Insemination – with or without stimulation with FSH
 IVF
◦ Patients with tubal pathology, patients who unresponsive
to above treatment
 Donor Egg with IVF
◦ Previous surgery/chemo with decreased ovarian function,
women whose egg quality is poor
Reference
 Gynaecology today
 Gynaecology by Ten teachers
 Medscape-subfertility
 http://www.who.int/topics/infertility/en/
 http://www.ivf-
infertility.com/infertility/investigations/female/laparoscopy.p
hp