INFERTILITY & ASSISTED

REPRODUCTIVE
TECHNOLOGY

Mujaahid Amin
Nafisyah Ruslan
Haashveeni Jayakumar
 DEFINITION
• WHO-ICMART (International Committee for Monitoring Assisted Reproductive Technology)

Infertility – a disease of the reproductive system defined by the failure to achieve a

clinical pregnancy after 12 months or more of regular unprotected sexual intercourse.

• Gynecology by Ten Teachers 20th edition

Subfertility – failure to conceive after regular sexual intercourse for one or two
years in the absence of any known reproductive pathology.
 Glossary
• Infertility: Lack of fertility after 1 year of frequent attempts

• Subfertility: A decrease, but not an absence, of fertility potential

• Sterility: Complete inability to achieve fertility

Hacker & Moore; Essentials Obstetrics and Gynaecology

Primary infertility
• When a woman is unable to ever bear a child, either due to the inability to
become pregnant or the inability to carry a pregnancy to a live birth (miscarriage
or stillbirth) without ever had a prior pregnancy.

Secondary infertility

• When a woman is unable to bear a child, either due to the inability to become
pregnant or the inability to carry a pregnancy to a live birth following previous
pregnancy or able to carry a pregnancy to a live birth.

WHO
- Prevalence worldwide; 50 million couples worldwide experience infertility.
- 2010, approximately 10.5% of women around the world experienced
secondary infertility, and roughly 2% experienced primary infertility.

Sarah Hodin; The Burden of Infertility: Global Prevalence and Women’s Voices from Around the World

- The fertility rate in Malaysia is continuing to decline — it is at 1.8 babies per

woman, well below the replacement level of 2.1 babies — according to the
latest figures released by the Department of Statistics.
The News Strait Times, Oct 29 2019
 STIGMA CIRCULATING INFERTILITY.
- In many cultures, women who do not have children suffer from
stigmatization, discrimination and ostracism, even if the underlying
cause lies in their male partners or husbands,

- this falls disproportionately on women. Men tends to blame women

and seek other partner.
 Natural Conception
• For women with normal
menstrual cycle of 28 days,
ovulation occur around D14.

• Average survival time of oocyte is

24 hours, while after ejaculation
sperm may survive for up to 7
days in female reproductive tract.
 General causes affecting natural conception
• Age >35 years old - decline oocyte quality and quantity
• Smoking – reduces fertility in women and semen quality in men
• Coital frequency – 2-3x per week
• Alcohol – excessive alcohol intake affects sperm quality, harmful to foetus
• BMI – (<18.5) and (>24.9) will have difficulty in conceiving
• Drugs – NSAIDS inhibits ovulation, chemotherapy drugs destroy rapidly dividing cells eg: gametes
• Occupational hazards – chemicals and radiation

Pre-conception :
Life style
Pre-conception folic acid 3 months prior up to 12 weeks POG – neural tube defect
Rubella screening; vaccination 3-6 months prior – avoid congenital rubella syndrome
ETIOLOGY
INFERTILITY

MALE CAUSES (30%) FEMALE CAUSES

• Disorder of spermatogenesis • Ovulatory factor
• Impaired sperm transport • Tubal factor
• Erection and ejaculation problem • Endometrial factor

Unexplained Infertility
(25%)
 1. Ovulation Problems
• Ovulation is regulated by Hypothalamus, Pituitary and Ovary (HPO) axis.

• Function of HPO is disrupted in cases:

- BMI <19 or >29 (underweight or obese)
- Polycystic Ovarian syndrome (PCOS)
- hyper/hypothyroidism
- hyperprolactinemia
Polycystic Ovarian Syndrome (Revised Rotterdam criteria 2003)

• commonest cause of anovulation

- Menstrual irregularities (oligo/amenorrhea)
- Hirsutism, acne, overweight, increased risk of metabolic syndrome
- USG : polycystic ovaries (>12 follicular cysts <10mm)

 Anti Mullerian hormone (AMH) level – quantity of ovarian follicle pool,

act as marker of ovarian reserve – increased in PCOS patients.
 2. Tubal factor
• Tubal blockage due to:

 previous pelvic inflammatory infection (PID) –

Chlamydia infection

 inflammation within abdominal/pelvic cavity –

internal adhesions

 scarring and adhesion secondary to surgery or

endometriosis

• Partial or complete tubal blockage

3. Endometrial factor
• Abnormalities within endometrium – prevents successful implantation
• Causes – presence of mass (fibroids, polyps), intrauterine adhesions (D&C, Asherman’s
syndrome), uterine abnormalities
Causes of Male Infertility

Hypothalamic pituitary disorder

Testicular disease

Disorder of sperm transport

idiopathic
Hypothalamic Pituitary Disorder
Congenital : Kallmann’s Syndrome
• Rare genetic d/o due to isolated deficiency of GnRH characterised by
late/absence of sigs of puberty along with absent/impaired sense of
smell
Acquired : Pituitary tumor ; pituitary microadenoma,
craniopharyngioma and surgical or radiation treatment of these lesion
 impaired secretion of gonadotropins
Systemic : obesity, DM , sleep apnea
• Tends to have low testosterone
Testicular disease (related to sperm
production)
• Congenital ( Cryptochirdism )
• Chromosomal ( Klinefelter’s )
• Germinal cell aplasia ( Sertoli cell only syndrome )
• Infection
• Trauma
• Drugs
• Chemotherapy/radiotherapy
• Environmental factors
Testicular disease
Congenital : Cryptochidism
• Failure of one or both testes to descend into scrotum
• Men with history of undescended testes have lower sperm counts, sperm
of poorer quality, and lower fertility rates than men with normally
descended testes.
• Impaired spermatogenesis in the undescended testis is probably related to
underlying genetic, hormonal, and developmental abnormalities, some of
which may be partially reversible through early surgical intervention.
• Sperm counts in adulthood are directly related to prepubertal germ cell
counts and type of cell at the time of orchiopexy
Testicular disease
Chromosomal : Klinefelter’s syndrome – extra X chromosomes
• S&S of androgen deficiency (gynecomastia, sexual dysfunction, or
osteoporosis)
• Typically have small testes d/t progressive fibrosis and destruction of
both functional (steroidogenic and spermatogenic) compartments of
the testes  reduced amount of testosterone  azospermia
Testicular disease
Germinal cell aplasia : Sertoli cell only syndrome
• Condition in which only Sertoli cells lined the seminiferous tubules in testis
 no sperm cell  no sperm production (azoospermia)
Infection : mumps orchitis
• Infertile due either to germinal cell damage, ischemia, or the immune
response to the infection
• Affected testicles may show a degrre of testicular atrophy  impair sperm
production
Trauma : testicular torsion
• Compression of spermatic vessels and impairs the spermatic blood flow 
impairs spermatogenesis  decreased sperm concentration
Testicular disease
Drugs
• Anabolic steroids such as testosterone used to build muscle and/or
decrease body fat
• Interfere with hormone signals to produce testosterone and to
produce sperm  men’s natural testosterone stop producing  drop
in level of testosterone
• Recreational drugs – marijuana, cocaine, impair production of healthy
sperm
• Antihypertensive, antidepressant and some sedative cause impotence
and may depress sperm count and motility
Testicular disease
Environmental factors
• Smoking - Increase reactive oxygen species (ROS) results in oxidative
stress significant affect on sperm ( reduce sperm concentration,
motility and morphology)
• Hyperthemia – tight underwear, hot baths /sauna
• small increases in testicular temperature accelerate germ cell loss
through apoptosis
Chemotherapy/radiotherapy
• Chemo affects number of sperm produce, ability to fertilise the egg
• Radiotherapy kills stem cells producing sperm
Disorder Of Sperm Transport
Infection causing obstruction of vas deferens
• Epididymitis- inflammation of the epididymis( function as transport, storage and maturation
of sperm cell )
Erectile dysfunction
• consistent or recurrent inability to achieve or sustain erection of sufficient rigidity and
duration during sexual intercouse  impairs the transport of semen
• Risk factors – DM, HPT, obesity. Dyslipidemia, cvs disease, smoking and medication –
antiepileptic, antihypertensive, psychotropic drug
Retrograde ejaculation
• Entry of semen into bladder instead of going out through urethra
• Surgery causing damage of muscle to the bladder or nerves controlling the muscle
Vasectomy- surgical procedure for male sterilization

Congenital bilateral absence of vas deferens

Approach to patients with subfertility
Female Male
• Length of time spent trying for • Length of time spent trying for
pregnancy pregnancy
• Any previous pregnancy
• Fathered any previous pregnancy
• Coital frequency
• History of mumps or measles
• Occupation
• History of testicular trauma, surgery
• Menstrual history
to testis
• History of PID
• Occupation
• Medical and surgical history
• Previous fertility treatment • Medical and surgical history

• Cervical smear history

• General health eg: thyroid disorder
 Physical examination
Female Male
• General examination • General appearance
 BP, pulse, height, weight • Tanner staging
• Thyroid • Testicular examination
• Tanner staging  Volume
• Breast examination  Consistency
 galactorrhea  Masses
 Absence of vas deferens
• Pelvic examination  Varicocele
 uterine pathology  Surgical scars
INVESTIGATION FOR
INFERTILITY
• In a couple that has not conceived after 1 year of regular,
unprotected intercourse

• Investigation done earlier in couple with history of predisposing

factors:-
 amenorrhea/oligomenorrhea
 pelvic inflammatory disease
 woman with low ovarian reserve
 known male factor subfertility

• The interval is however, shortened to 6 months after the age of
35 years of the woman and 40 years of man.
 It is important that both partners should
come at the first visit.
 Detailed general and reproductive history
should be taken in presence of both.
 Clinical examination of each partner is
carried out separately.
 No one is to be blamed !
INVESTIGATIONS FOR INFERTILITY
1. Hormonal investigations – FSH, LH, Estradiol, Testosterone,
Progesterone, TSH, Prolactin
2. Imaging studies – pelvic ultrasound, hysterosalpingography, saline
sonography
3. Diagnostic laparoscopy
4. Semen analysis
5. ***Infection screen
1ST LINE INVESTIGATION

• Normal; asymptomatic patient- do screening first

• Pros: Non-invasive,convenient.

1) HORMONAL INVESTIGATION
• Female: FSH, LH, estradiol, testosterone and TSH (day 2-3 menstrual cycle)
Prolactin and progesterone-mid-luteal phase(day 20-22)
• Male : FSH, prolactin and TSH

2) PELVIC ULTRASOUND – to access uterine size & pathology, adnexal masses

3) SEMEN ANALYSIS ( after 2-3 day period of abstinence of sexual intercourse)
4) +/- INFECTION SCREEN- to access for PID in female
1) HORMONAL INVESTIGATION
Female
• Day 2-3 of menses : serum FSH, LH, estradiol ( to asses the ovarian reserve of oocytes)
* testosterone - PCOS
*TFT - Irregular menstrual cycle
• Day 20-22 : mid-luteal phase prolactin and progesterone ( confirm ovulation )
*Progesterone > 5-10ng/ml indicates ovulation had occurred in this cycle
* Prolactin -If amenorrhoea, oligomenorrhoea or galactorrhoea

Male : FSH- elevated level indicates substantial testicular parenchymal damage

: prolactin – for hyperprolactinemia
: TFT for hypothyroidism
2) PELVIC ULTRASOUND
-to access uterine size & pathology (fibroids, polyps, congenital
anomaly)
-to access adnexal masses (endometrioma, PCOS)
 3) SEMEN ANALYSIS

• Assess the number, morphology and motility of

spermatozoa
• Ideally, performed after 2-4 days of sexual abstinence
• Pt is asked to provide sample (usually by
masturbation)
• Specimen should be analysed within 2 hours of
production, keep warm and away from spermicidal
agents
• At least two samples should be collected at least one
week apart
• WHO Reference Limits
• Not normal semen parameters but these values represents the generally
accepted 5th percentile derived from study of men whose partners conceived
within one year
• Semen values that fall below these reference ranges are not necessarily
infertile Parameter Lower Reference Limit

Semen Volume ≥1.5ml

pH 7.2

Total Motility 40%

Sperm Concentration ≥15 million spermatozoa per

ml

Progressive Motility ≥32%

Sperm Morphology ≥4% normal forms

• If initial sample is below reference limits – repeat test ideally after one full cycle of
spermatogenesis (74 days / 3 months)
• If severe abnormalities (azoospermia or severe oligozoospermia) – repeat test 2-4 weeks later
• Men with a normal semen analysis
• Male partners in an infertile couple may have idiopathic male infertility
• Other possibilities include infertility of the female partner or a couples' infertility factor
• Men with an abnormal semen analysis
• Normal sperm concentration, abnormal morphology and/or motility
• Referral to a specialist in ART such as intracytoplasmic sperm injection (ICSI) might be useful
• Sperm concentration <10 million/mL
• Because Klinefelter syndrome is common in men presenting with infertility and sperm concentrations
<10 million/mL, serum total testosterone (on a blood sample obtained between 8 and 10 AM), serum follicle-
stimulating hormone (FSH), and luteinizing hormone (LH) measurements should be performed
• Severe oligozoospermia or azoospermia
• Need endocrine testing and genetic testing
• Require transrectal ultrasound for evaluation of obstructive azoospermia (those who have normal endocrine
testing, normal testicular volume, palpable vas deferens on examination, and azoospermia)
 2nd LINE INVESTIGATION
HYSTEROSALPINGOGRAGHY (HSG)
• Radio-opaque aqueous solution injected through cervix under X-Ray control to
assess uterine cavity and patency of fallopian tubes
• Done within first ten days of menstruation - to avoid risk of inducing ectopic
pregnancy or inadvertent exposure of early embryo to ionizing radiation
• Free spills of dye from both fallopian tubes confirms patency
• Identify developmental or acquired abnormalities of the uterine cavity that
negatively impact fertility, such as submucous fibroids, a T-shaped cavity, polyps,
and congenital Müllerian anomalies
• High specificity and sensitivity for diagnosing distal tubal occlusion or major distal
tubal adhesions, but much lower specificity for diagnosing proximal tubal
occlusion
• dye flow freely to into abdominal
cavity – patent tubal
• Dye spills loculated or tube appear
tu be in abnormal position position
– peritubal adhesion
• Filling defets- terine adhesion and
submucous fibroid
3RD LINE INVESTIGATION
DIAGNOSTIC LAPAROSCOPY
• Invasive and expensive
• Indicated in women having endometriosis or suspected pelvic adhesions or tubal disease
(physical examination, HSG, or history)
• Tubal patency is tested by injection of methylene blue through cervix and observing spillage of
dye from fimbrial end
• Advantages
• Surgical therapy can be initiated, while avoiding potentially ineffective or unnecessary
empiric medical treatment
• Endometriosis, if identified, can be excised or ablated at the time of the diagnostic
procedure, and pelvic adhesions can be lysed
 MANAGEMENT
MALE FEMALE
LIFESTYLE MODIFICATION
Body mass index of 20–24 is optimum , especially women with PCOS
Smoking or alcohol consumption is to be avoided.
Advice to have intercourse during the midcycle
Psychotherapy to improve the emotional causes, if any
MEDICAL MANAGEMENT
Hypogonadotropic-hypogonadism -hCG 5000 IU Normogonadotropic—normoprolactinemic patients who are
intramuscularly ( 1-2x/week ) having normal cycles with absent or infrequent ovulation –
pure FSH (75–150 IU) is added to hCG when there is no Clomiphene citrate
sperm in the ejaculate with hCG alone
Hyperprolactinemia – dopamine agonist - cabergoline PCOS cases with oligomenorrhea or amenorrhea. The
estradiol level should be > 40 pg per mL. – Clomiphene
citrate
Kallmann’s syndrome – Pulsatile Gnrh therapy via minipump Hypothalamic amenorrhea following stress or ‘pill’ use. –
infusion Clomiphene citrate
Retrograde ejaculation - phenylephrine (a-adrenergic PCOS , BMI > 25 kg/m2 , insulin resistant - Metformin
agonist) is used to improve the tone of internal urethral
sphincter
MALE- FEMALE
MEDICAL MANAGEMENT
Erectile dysfunction - sildenafil (25–100 mg) or tadalafil Obese patients with subclinical hypothyroidism - Eltroxin
(10–20 mg) 0.1 mg
Pre-existing or induced elevated androgens -
dexamethasone 0.5 mg daily for 10 days, starting from 1st
day of cycle
Elevated prolactin level with or without galactorrhea-
Bromocriptine or cabergoline (dopamine agonist)
therapy
SURGICAL MANAGEMENTS

obstruction of vas - vasoepididymostomy or polycystic ovarian syndrome - Laparoscopic ovarian

vasovasostomy drilling (LOD)
Surgery for pituitary prolactinomas

Surgical removal of virilizing or other functioning ovarian

or adrenal tumor
Peritubal adhesions - salpingo-ovariolysis either by
laparoscopy or by laparotomy
Proximal, mid, distal tubal block – Tubal surgery
Male Female
submucous fibroid - Myomectomy
uterine synechiae - Adhesiolysis (Hysteroscopic)
Endometrial polyps - Hysteroscopic polypectomy
Obesity -Bariatric Surgery
• Clomiphene citrate
Selective estrogen receptor modulator
Anti-estrogenic as well as weakly estrogenic.
Mechanism of action: It blocks the estrogen receptors in the hypothalamus 
increased GnRH pulse amplitude increased gonadotropin secretion ( LH &
FSH ) from the pituitary to stimulate follicle growth The negative feedback of
endogenous estrogen is thus prevented .
Anti-estrogenic effects are seen on the endometrium and on the cervical mucus
(becomes thick and viscid and it hinders sperm penetration )
Side effect : visual disturbances, headache, hot flushes, breast tenderness,
abdominal discomfort, loss of hair, rashes and ovarian enlargement and
multiple pregnancy
Clomid taken from day 2 – 6 of menstruation. ( dosage : 50 - 150mg daily )
• Aromatase Inhibitors
Mechanism of action : inhibits the enzyme aromatase in the granulosa cells of
ovarian follicles suppress estrogen
used either as a first line therapy (alternative to clomiphene) or in clomiphene
resistant women (p. 245) with anovulatory infertility
Letrozole 2.5 mg given from D3 to D7 increases the release of gonadotropins
from the pituitary and stimulates development of ovarian follicle
• Gonadotropins
Indication : Hypogonadotropic hypogonadism, Clomiphene failed or resistant
cases, Unexplained infertility, Sub-fertile women who are elderly.
GnRH agonist - down regulation of pituitary gland by desensitization of pituitary
GnRH receptors
GnRH antagonists—can block pituitary GnRH receptors completely without any
initial stimulation (flare effect)
Mechanism of action : stimulate follicles growth.
Assisted reproductive
technologies ( ART )
 What is ART ?
• Procedures that involve manipulation of gametes and embryos outside the body for
the treatment of infertility.

• Methods of assisted reproductive technologies :

- Intrauterine insemination
- In vitro fertilization ( IVF )
- Intracytoplasmic sperm injection ( ICSI )
- Zygote Intrafallopian Transfer - Oocytes are collected and fertilised
in vitro; the resulting zygote is placed into the fallopian tube.
- Gamete Intrafallopian Transfer - Oocytes and sperm are
placed in the fallopian tube under laparoscopic
/hysteroscopic guidance
- Surrogacy
Intrauterine Insemination
• A type of fertility treatment whereby better-
quality sperm are separated from sluggish,
non-moving or abnormally shaped sperm and Indication Contraindication
then injected directly into the womb. Hostile cervical mucus endometritis

• Bypass the abnormal endocervical canal with Cervical Stenosis bilateral tubal
obstruction
increased concentration of motile sperm as
Immune factor (male and female) severe oligospermia.
close to the fallopian tubes.
Oligospermia or asthenospermia Amenorrhea

Male factor—impotency or anatomical defect cervicitis

(hypospadias) but normal ejaculate can be
obtained

Unexplained infertility cervical atresia

 Procedure
• Male partner produces semen on the day of treatment by masturbation after 2-7 days sexual abstinence
• Prior to IUI, it is necessary to remove seminal plasma to avoid prostaglandin-induced uterine contractions.
Insemination with unprocessed semen is also associated with pelvic infection
• The most frequently used methods involve centrifuging spermatozoa through culture medium or density
gradients followed by re-suspension in suitable culture media
• The sperm suspension can be deposited in the cervix, the uterus, the peritoneum or the Fallopian tube
• The processed motile sperm count for insemination should be at least 1 million and best results are obtained
when the motile sperm count exceeds 10 million.
• Introducing a 0.2 –0.5 ml sperm suspension into the uterus with a small flexible polyethylene catheter, usually
without imaging guidance.
• Fallopian tube sperm perfusion (FSP), the inseminate is 4 ml, with an attempt to seal the cervix to prevent
semen. This large volume of fluid may fill not only the uterine cavity and Fallopian but results in a sperm flushing
of the Fallopian tubes and an overflowing of the inseminate into the pouch of Douglas, and may even end up
inside the peritoneal cavity . May flush the ova out of the tubes or induce abnormal myosalpingeal contractions
resulting in expulsion of the ova from the tube with subsequent failure of fertilization
• Insemination is done 32–36 h following hCG administration.
• Procedure may be repeated 2–3 times over a period of 2–3 days.
 For women aged under 35, about 18% of IUI cycles
result in a healthy baby being born (a cycle is one full
round of IUI treatment).

Women aged 35 to 37 have a 14% success rate

How
successful is Women aged 38-39 is 12% success rate .
one cycle of
IUI ? For women over 40, your chances are lower (5% for
women aged 40 to 42 and 1% for women aged over 42)

On average a women needs around 3-6 cycles.

 In-Vitro Fertilization ( IVF )
• ‘fertilisation in glass’.
• First IVF baby : Louise Brown in 1978 in United Kingdom , followed by
Aus in 1980 and New Zealand in 1983.
• First IVF baby in Malaysia : 1987
• It is estimated that over 3.75 million babies have been born worldwide
using ART since 1978 following the birth of the first in vitro fertilisation
(IVF) baby.
• The process includes stimulation of ovaries with gonadotrophins
followed by oocyte collection, fertilisation in vitro in the laboratory
and subsequent embryo transfer within the uterus
Stages of IVF –up to 2/12
 1. OVARIAN STIMULATION IN AN ART CYCLE
• Gonadotrophin stimulation
• Factors influencing dose of FSH : The daily dose of gonadotrophins depends
on ovarian reserve. The aim of stimulation is to produce an adequate
number of oocytes without hyperstimulation.
• In young patients with good ovarian reserve : 150 iu
• In older women and/or those with poor ovarian reserve : 300 iu
• Women who are overweight or obese require 20% higher doses of
gonadotrophins
• PCOS : 150 iu ( the dose of gonadotrophins has to be very carefully titrated
as there is a very narrow therapeutic window between over- and
underresponsed
• Pituitary suppression
GnRH agonists
• Pituitary suppression takes at least 7–10 days to establish. Use of GnRH agonists
improves success rates compared with stimulation with gonadotrophins alone.
• Long protocol - administration of GnRH agonist for at least 14– 18 days to
achieve maximal suppression of ovarian activity before commencing
gonadotrophin administration
• long follicular protocol - use of GnRH agonist from the first day of the cycle
• long luteal protocol - GnRH agonist administration from the mid-luteal phase of
the previous cycle
• Gonadotrophins are commenced after at least 2 weeks of GnRH agonist
• The agonists are continued up until the day of the last dose of gonadotrophins,
which is usually the day of human chorionic gonadotrophin (hCG) administration
– the ovulatory trigger.
• Short protocol - GnRH agonist is started at the same time as gonadotrophins –
day 2 of the menstrual cycle & continued up until the last day of gonadotrophin
injections – the day of hCG administration.
• Ultra-short protocol - GnRH agonist is commenced a day before gonadotrophin
injections and is given only for 3 days. Gonadotrophins are continued alone after
that. These regimens are usually recommended for those patients in whom a
suboptimal response to gonadotrophins is expected ( poor responder )
• GnRH antagonists
• compete directly with endogenous GnRH for receptor binding  rapidly inhibit
secretion of gonadotrophin and steroid hormones.
• Unlike agonists, antagonists produce immediate profound suppression of LH;
that is, within hours of administration
• Gonadotrophins are started on day 2 of the cycle, followed by the antagonist on
day 6 or when the leading follicle reaches a diameter of 14mm, whichever is
earlier.
• Dose for GnRH antagonist administration is 0.25mg
• In addition, there is a significant reduction in the risk of OHSS when antagonists
are used.
• Cycle monitoring
follicle tracking with ultrasound and ovarian steroid measurement
The reasons for monitoring are to identify women at risk of ovarian
hyperstimulation early in stimulation and to reduce their dose.
• Ovulatory trigger
HUMAN CHORIONIC GONADOTROPHIN
Once the follicles are mature, hCG is given to facilitate final maturation of the
oocyte.
Oocyte retrieval is usually scheduled 34–36 hours after administration of hCG.
2. OOCYTE RETRIEVAL
The advent of transvaginal ultrasound-guided aspiration techniques rendered
the procedure simpler, safer and more efficient. Vaginal ultrasound is used to
visualise the maximal diameter of each follicle, allowing the needle to enter
the centre of each follicle.
Give appropriate analgesia/anesthesia
3. FERTILISATION
After oocyte retrieval, freshly ejaculated seminal fluid is prepared to
concentrate motile spermatozoa in a fraction that is free of seminal plasma
and debris.
Insemination is usually performed 40 hours after hCG administration, with
each oocyte inseminated with 50 000–200 000 motile spermatozoa. For
conventional IVF, all oocytes that are obtained are inseminated. There is no
need to clean the oocytes before insemination.

The rate of normal fertilisation after conventional IVF is about 60% per
inseminated oocyte
Intracytosplasmic sperm injection
• ICSI was first introduced in 1992 for severe male factor infertility
• The indications for ICSI are:
 low count /azoospermia and or low motility
Obstructive & non-obstructive azoospermia.
 severe deficits in semen quality
 previous failed fertilisation (a previous IVF treatment cycle has resulted in
failed or very poor fertilisation)
 previous low fertilisation
low number of oocytes
older women
• Before carrying out ICSI, the oocytes have to be cleaned and denuded of
all surrounding cells. The mature oocytes (metaphase II), are then
selected and injected with a single sperm
• Insemination is performed 40–42 hours after hCG administration.
• Thereafter, following an incubation/injection period of 16–18 hours in
culture medium, oocytes are examined to ensure that normal fertilisation,
as defined by the presence of two pronuclei, has occurred. Cell division
ensues, usually reaching the four-cell stage by day 2 and the eight-cell
stage on day 3
• Embryos are maintained in culture within an incubator at a constant
temperature of 37°C and a humid atmosphere containing 5% CO2.
• high-quality embryos are selected for transfer to maximise the chance of
conception
• If only one oocyte is fertilised, embryo transfer can be performed on day 2
(day 0 being day of oocyte collection). If two or more embryos are
available then culture to day 3 is usually recommended and the best single
embryo may be selected for transfer at that point
• Embryos are placed within the endometrial cavity just below the fundus of
the uterus, using a soft catheter. Pregnancy rates per blastocyst transfer
can be as high as 60%. If embryo transfer is carried out under ultrasound
guidance, a higher ongoing pregnancy rate can be achieved
• LUTEAL PHASE SUPPORT REGIMENS
Recommended during IVF and ICSI to maximise implantation and pregnancy
rates
Progesterone is typically given for 2 weeks, although in some centres it is
continued up to 12 weeks of gestation.
Route - intramuscular, oral, rectal or vagina

The rate of normal fertilisation after ICSI is about 80% per inseminated
oocyte
HOW DOES IVF & ICSI DIFFER ?
• The only difference between the two is the way the egg is fertilised.
IVF allows the sperm to penetrate the egg of its own accord whereas
ICSI directly inserts the sperm into the egg
Consequences of treatment
• Two major complications of ART to consider are multiple pregnancy and
OHSS.
OHSS
OHSS is an iatrogenic complication of ovulation induction and ovarian
stimulation for ART and is characterised by multiple cystic enlargement of
the ovaries and rapid fluid shifts from the intravascular compartment to
the third space
Chemical mediators like cytokines, vascular epidermal growth factor (VEGF),
prorenin, renin and nitric oxide (NO) system are thought to be stimulated
with hCG administration  Increased capillary permeability  leakage of
fluid from the peritoneal and ovarian surfaces
Hx : abdominal distension, abdominal pain , nausea, vomiting , Dyspnea
MANAGEMENT OF OHSS
• Admit moderate – severe case Risk factors :
• To monitor complete hemogram, LFTs, RFTs, • Young age < 30 years,
electrolytes, coagulation profile, ECG and • PCOS
urine output. • Serum E2 >2500 pg/ml
• Chest X-ray (shielding the pelvis), monitoring • rapidly rising serum E2 levels
of O2 saturation is needed when there is (>75% rise from previous day),
respiratory compromise. ovarian ‘necklace sign’ on USG
• TVS is to be done to assess ovarian volume (multiple small follicles)
and ascites. • hCG administration
• Oral fluid is continued to prevent • multiple pregnancy.
hemoconcentration and to maintain renal
perfusion. Normal saline 150 ml/ hr IV is given
when hematocrit is >45 percent.
• To relieve respiratory distress, abdominal
paracentesis may be done under USG
guidance.
• Human albumin (50 ml of 25%) may be
administered to correct hypovolemia. It may
be repeated
• Pain is controlled with paracetamol or
pethidine.
• Intensive care management is needed for
specific complications like renal failure.
REFERENCES
• https://academic.oup.com/humrep/article/19/12/2721/2356326
• MRCOG and beyond by RCOG for infertility
• Nice guideline for infertility problem, treatment and assesment
• Intrauterine insemination The ESHRE Capri Workshop Group1