‫بسم هللا الرحمن الرحيم‬

Assisted reproductive technology-ART

• Definition: a range of techniques for

manipulating oocytes and sperm to
overcome infertility.
• The last resort for infertile couple is
the procedure of IVF & embryo
transfer.
 Who is eligible for ART?
1-Severe tubal disease, tubal blockage.
2-Severe endometriosis.
3-Unexplained infertility.
4-Unsuccessful IUI.
5-Individuals with male factor infertility
( abnormalities in sperm production, e.g. in men with
less than 10 million motile sperm, abnormalities in
function or transport or prior vasectomy)
 Abbreviations used in ART

IVF ------------------ In vitro fertilization

IUI -------------------intrauterine insemination
PGD-----------------preimplantation genetic diagnosis
DI ------------------- donor insemination
GIFT -----------------gamete intrafallopian transfer
ICSI -----------------Intracytoplasmic sperm injection.
MESA ------------microepididymal sperm aspiration.
In vitro Fertilization (IVF) Procedure
A procedure whereby an egg (or more than one
egg) is retrieved from the body of a woman
and combined with sperm outside the body to
achieve fertilization.
If fertilization is successful, the fertilized egg
continues to develop an embryo, which is
subsequently transferred back into the uterus/
fallopian tube.
If many embryos develop some of the surplus
embryos may be frozen and used later.
 A typical IVF- embryo transfer cycle

1-Initial consultation.
2-Pituitary down regulation.
3- ovarian stimulation.(superovulation).
4- Ovulation trigger with hCG.
5-Oocyte collection.
6-Insemination of Oocyte(fertilization).
7-Embryo transfer.
8-Luteal support.
9-Pregnancy test.
 1- Initial consultation

Initial consultation involves a detailed

history & examination, which provides an
opportunity to assess the cause of
subfertility & the most appropriate
treatment technique.
Investigations prior to assisted reproduction:
1. Hormone profile: AMH, FSH,
E2(measuremenrt of ovarian reserve),
progesterone (check of ovulation).
2. Semen analysis.
3. Pelvic ultrasound.
4. Evaluation of uterine cavity and fallopian
tubes: HSG, laparoscopy and hysteroscopy.
 Investigations prior to IVF
Female
1- Tests of ovarian reserve.
What is Ovarian Reserve?
As a woman ages, the follicles gradually declines
over time until they are depleted at menopause.
Screening for ovarian reserve is a fundamental
part of the initial evaluation for infertility
patients.
In general, the greater the number of remaining
follicles, the better the chance for conception.
For patients with low ovarian reserve, implantation
rates are generally poor and the possibility of
successful pregnancy is very limited.
The tests
A- FSH, E2 ( early follicular phase-day3 ).
B-Anti-Mullerian hormone (AMH) which is more
accurate test to assess ovarian reserve.
 AMH
Is produced by granulosa cells.
It represet the quantity of ovarian follicle
pool, a useful marker of ovarian reserve,
also a useful predictor of ovarian responce
to gonadotropin stimulation for IVF.
Serum AMH decrease with age,& is
undetectable in postmenopausal period.
C- Antral follicle count by TV/US

a combination of AMH and a transvaginal

ultrasound to count the number of antral
follicles is probably the best way to assess
ovarian reserve and future fertility.
2- if irregular priods: prolactin, TFT, testosterone, SHBG.
3- screening for hepatitis B, hepatitis C & HIV.
4- transvaginal ultrasound indicated for :
A- ovarian volume & antral follicle count.
B- presence of ovarian cyst.
C- assess ovaries for accessibility for transvaginal oocyte
retrieval(TVOR).
D-assess the uterus(e.g.fibroid).

MALE (Seminal fluid analysis)

- to assess the best way to use the sperm, generally IVF
if parameters are good, & ICSI if severe problem.
2- Pituitary down-regulation
is essential to prevent a natural LH surge
during follicular stimulation as this would
result in follicular rupture prior to egg
retrieval. This is by using GnRH agonist, or
GnRH antagonists.
• A low serum oestradiol level ( <100 u/L)
or thin endometrium on U/S scan are
used to confirm down-regulation of the
pituitary.
3- ovarian stimulation with daily FSH to produce 8-10
follicles- (18mm).

4- Ovulation trigger with hCG.(induction of ovulation

by hCG).

5- oocyte retrieval.( the follicles can be collected

during an ultrasound guided procedure via a very
fine needle).
• Using a microscope, the embryologist identifies the
oocyte removed in the follicular fluid & then
transfer these to culture medium in an incubator.
• During the sperm preparation, the
sperm sample is washed to remove
the seminal plasma, leukocytes &
bacteria. The motile sperm can be
selected for use in the insemination
process.
6- Fetrilization (the prepared sperm is mixed with
the oocytes & incubated for IVF.
• For ICSI a single sperm is injection into the
cytoplasm of each oocyte.
Indications for ICSI
1- severe male factor infertility(azoospermia &
subsequent surgical sperm retrieval(SSR) by, for
example, microepididymal sperm
aspiration(MESA).
2 - poor or total non fertilization from previous IVF.
Whatever the process of insemination, the
next stage involves incubating the
oocyte with the sperm for 16-18 hours.
7- Embryo transfer(the fertilized
embryo(s) is then replaced into uterine
cavity(2nd, or 3rd day of culture).
• Any spare embryos of good quality can be
subjected to embryo cryopreservation,
with liquid nitrogen for use in a frozen
embryo replacement cycle in the future.
The embryos can remain in storage
without deterioration until they are
required, they will undergo a thawing
process with two-thirds of embryos
surviving the procedure.
8- Luteal support.
using hCG, progestogens, 2-12wk).

9- Pregnancy test.
Pregnancy is detected by urinary pregnancy
test or by analysis of the serum beta-
hCG14 days after embryo transfer.
 Intrauterine insemination

It involves the placement of a sample of prepared

sperms in the uterus using a cannula, at the time
of ovulation.
It is most successful if it is combined with ovarian
stimulation to produce up to 2 mature follicles.
Close monitoring of the treatment is essential as
there is a high risk of multiple pregnancy.
It is used to treat mild male factors subfertility as
well as unexplained subfertility, cervical problems,
ovulatory disorders, mild endometriosis.
it requires at least one healthy fallopian tube.
 Gamete intrafallopian transfer(GIFT)
a laparoscope is used to transfer the eggs & sperms to
the fallopian tube.
Advantage:
1- This allows fertilization to occur in the natural
location.
2- Require minimal laboratory facilities.

Disadvantage
1- Requires laparoscopy under general anesthesia.
GIFT is infrequently performed now, because IVF has
become more successful.
Cryopreservation of gametes

• Sperm or oocytes can be cryopreserved

for later use(e.g. patients undergoing
chemo/radiation therapy for cancer).
 Preimplantation genetic diagnosis

A form of a very early prenatal diagnosis, to detect

genetic disease in the embryo at the
preimplantation stage.

It allow couples carry serious genetic disorders to

have embryos free of these diseases, and
prevent the need for invasive prenatal diagnosis
later and the difficult decision to terminate the
pregnancy.
 Human Fertilization and Embryology Authority
HFEA

• an organization to control and review research

involving embryos. It maintains a register of
persons whose gametes are used for assisted
conception.
• All assisted conception centers in the UK
involved in treatment, research of the storage
embryos, must be licensed by the HFEA.
 Complications of assisted conception(ART)
1- Ovarian hyperstimulation syndrome(OHSS)

Definition
An iatrogenic condition that can occur in any IVF
cycle. It is characterized by an excessive ovarian
responce→multiple follicular growth.
Severe OHSS can be life threatening.
Women at risk
1- Young patients with polycystic ovaries.
2- women who develop 20 or more follicles .
It appears usually after the
administration of exogenous hCG or
after the natural rise in hCG with
conception.

Patients presents with abdominal pain &

distension, nausea, bowel disturbance,
shortness of breath & poor urinary output.
Severe OHSS can be life threatening & is
associated with intravascular fluid
depletion, thrombosis, ascites & pleural
effusion.
Management
the cycle is abandoned & then restarted at a lower
dose,
or the eggs collected, fertilized & then all the
embryos electively frozen as severe OHSS tend to
be most severe in patients who become pregnant .
These patients may require in patient care by a specialist
team.

1- hospital admission.(monitor fluid balance).

2- if ascites, it can be drained on a daily basis, 1
litre/day, give symptomatic relief & increase
UOP.
3- if pleural effusion, tapping.
4- because of risk of thromboembolism,
thromoprophylaxis given(antithrombotic
stockings & LMWH daily).
2- Ectopic pregnancies: incidence with IVF is 4%.
With the increasing amount of salpingectomies
performed for hydrosalpinges, it is hoped that
the incidence of ectopic pregnancies with IVF will
reduce.

3- Transvaginal oocyte retrieval complications:

infection of ovaries, ovarian abscess, damage to
bowel ˂1%.
4- multiple births. IVF: 24%.
Assisted conception often result in twin or higher
order pregnancy.
HFEA regulations prevent the transfer of more than
two embryos except in exceptional
circumstances(e.g.if the age is 40 years or more).
Multiple pregnancies have increased morbidity &
mortality for both the mother & the babies, with
enormous healthcare costs.
In Scandinavian countries, women less than 35
years→ single ET.
Other embryos are frozen.