Assisted reproductive

technology

Edited by:-
❖ Assisted reproductive technology (ART):-
Assisted reproductive technology includes medical procedures which
are primarily used to address infertility , ART involve procedures such as
intrauterine insemination, in vitro fertilization (IVF), intracytoplasmic sperm
injection (ICSI), cryopreservation of gametes or embryo and the use of fertility
medication. ART can be also referred to as fertility treatment if it's mainly
belongs to the field of reproduction endocrinology and infertility.

Some of ART may be used with regard to fertile couples for genetic
purpose and may also in surrogacy arrangement, but not all surrogacy
arrangement involve ART.
• Intrauterine insemination (IUI):

One of the techniques that’s commonly used to treat infertility is IUI,

the fallopian tubes must be assessed before this procedure to role out scarring or
endometriosis , as the fertilization of the oocyte by

a sperm occurs within these tubes.

▪ Basic steps of IUI:-

1. Initial ovulation induction with clomiphene citrate
While intercourse is timed.
2. Monitoring woman's ovulation using various
self-testing or imaging techniques.
3. Collecting sperms from male partner and washing
them to be finally injected in the uterus of the
woman.
- If three cycles have been passed and pregnancy didn’t occur, we continue
to stimulate ovulation using clomiphene to another three cycles.
- If the second time failed and no pregnancy occur ovulation is stimulated
by gonadotropin stimulating hormone followed by IUI.
- If the previous failed we will probably lead to IVF.
• In vitro fertilization (IVF):

It’s a series of complex procedures which are

used to help with fertility or prevent genetic
problems. It’s the most form of

assisted reproductive technology in which mature

eggs are collected from ovaries and then fertilized

by partner sperm in a liquid at the laboratory. The

chance of having a healthy baby using IVF depends
on some factors:-
1. Your age and the cause of infertility.
2. Cost and time.

If IVF is performed to treat infertility, partners will be able to try

treatment options before attempting IVF which include fertility drugs which
increase production of eggs or intrauterine insemination. Sometimes IVF is
applied as a primary treatment for infertility in woman whose age is over 40 or
have certain health conditions for
example:

• Fallopian tube damage or blockage.

• Ovulation disorder or Endometriosis.
• Endometriosis or previous tubal
sterilization or removal.

After fertilized egg (zygote) undergoes IVF

embryo culture for 2-6 days in the
woman's uterus with intention of establishing
a successful pregnancy. However without
additional techniques the possibility of
pregnancy would be rare. So there are some
additional techniques which are majorly used
in IVF which includes:-

1- ovarian hyper stimulation to generate

multiple eggs.

2- Ultrasound guided transvaginal oocyte

retrieved directly from the ovaries .
Steps of IVF
3- Coincubation of eggs and sperms.

4- culture and selection of resultant embryos.

5- Embryo transfer into uterus.

1) Ovarian hyper stimulation:-

This process involve the induction of development of multiple follicles

of the ovaries. This way should be predicted by knowing some potential factors
that influence pregnancy using IVF as maternal age, duration of infertility or sub
infertility, bFSH and number of oocytes and level of anti-mullarian hormone.
The resulting prediction could be poor or hyper response to ovarian hyper
stimulation through that we can determine the protocol and dosage for ovarian
hyper stimulation.

There are several which are termed as natural cycle IVF:

• IVF using ovarian hyper stimulation, including gonadotropins, but with a
GnRH antagonist protocol so that the cycle is initiated from a natural
mechanism.
• Frozen embryo transfer: IVF using ovarian hyper stimulation followed by
embryo cryopreservation and then embryo transfer in a later natural cycles.
• IVF using no drugs for woman whose age ranges 40-42.
• Mild IVF, where a small dose of ovarian hyper stimulating drugs are used for
a short duration during a woman natural cycle aiming at producing 2-7 eggs
and creating healthy embryo.

- Final maturation induction:

As the ovarian follicles have reached a certain degree of development

induction of final oocyte maturation is performed by injection by human
chorionic gonadotropin (HCG) , it acts as an analogue of luteinizing hormone
and ovulation would occur between 38-40 hours after a single HCG injection.

2) Egg retrieval :-
 After 34-36 hours after HCG, just prior to follicle rupturing eggs are
retrieved from the patient using a transvaginal technique called transvaginal
oocyte retrieval, involving an ultrasound needle
which is pierced at the vaginal wall to reach the
ovaries. Through this needles follicles can be
aspirated and the follicular fluid is passed to the
embryologist to identify

ova, commonly he removes between10-30 eggs.

This procedure usually takes between 20-40

minutes

depending on number of mature ovarian follicles,

it's done under conscious sedation or general

anesthesia.

- Egg and sperm preparation:-

Selection of the oocyte is applied prior to fertilization to select eggs that

can be fertilized as required eggs should be at metaphase(II) and if its
metaphase(I) , the oocyte can be kept being cultured so as to undergo posterior
sperm injection. In the meantime semen is prepared for fertilization by removing
inactive cells and seminal fluid in process called
sperm washing .

3) Co-incubation :-

The sperm and the egg are incubated together

at the ratio 75000:1 in a culture media in order for
actual fertilization. A review in 2013 shows that
incubation for 1to4 hours result a high significant
pregnancy than 16to24 hours , in both cases the egg

Demonstration of IVF
will be fertilized during co-incubation and will show two pronuclei.

-Intracytoplasmic sperm injection (ICSI) :

In a certain situation when men have low sperm

count or motility, a single sperm is injected directly

into the egg using ICSI then the fertilized egg is

passed to a special growth medium an left for about

48 hours until the egg consists of six to eight cells.

ICSI
4) Embryo culture:-

The duration of embryo culture is until cleavage stage (day 2 to 4 after co-
incubation) or the blastocyst stage (day 5 to 6 after co-incubation), embryo
culture until the blastocyst stage lead to a significant increase in live birth rate
per embryo transfer but this way wouldn’t confer a number of embryos available
for transfer

to control oocyte and embryo quality called time-lapse and embryo

cryopreservation.

5) Embryo selection:-

At the latest year precisely at 2009 laboratories

have developed grading methods microscopy system
for IVF, before that morphological scanning systems
is the best strategy for selection of embryos .

6) Embryo transfer:- The number of embryo to Time-lapse microscopy

be transferred depends on the number available,
the age and diagnostic factors. HEFA regulation said that a woman over 40 may
have up to 3 embryos but most clinics and country regulatory bodies seek to
minimize risk of multiple pregnancy. Embryos are transferred to the patient
uterus through a thin plastic catheter which goes through her vagina and cervix,
some embryos may be passed into the
uterus to improve chance of implantation.

-Luteal support:

It’s the administration of medication

generally by progesterone,progestin,hCG or GnRH agonists and often
accompanied by estradiol to increase the success rates of implantation and early
embryogenesis for completion and supporting the function of corpus leutum.

-Assisted zona hatching:

Assisted zona hatching can be performed shortly

before the embryo is transferred to the uterus, a small

opening is made in the outer layer surrounding the egg

in order to help the embryo hatch out and implantation

occur successfully.

Other assisted reproduction techniques:-

▪ Mitochondrial replacement therapy(MRT):

This process includes replacement of mitochondria
in one cell or more to prevent or ameliorate disease. MRT
is considered as a special form of IVF in which some or
the future baby’s entire mitochondrial DNA comes from
the third party. This technique is used in cases when
mothers carry genes for mitochondrial diseases.
 ▪ In gamete intrafallobian transfer(GIFT):
A mixture of sperm and eggs are placed directly in woman's fallopian tubes
using laparoscopy following a transvaginal ovum
retrieval.
▪ Reproductive surgery:

Treating fallopian tube and vas deferens

obstruction or surgical sperm retrieval(SSR) as the
urologist obtain sperm from the vas deferens,
epididymis or directly from the testes in a short
outpatient procedure.

❖ Risk factors of assisted reproductive technology:-

❖ Historical facts:-

The first successful birth of a child after IVF treatment was louis brown in
25th July 1978, the procedure take place at Dr.kershaws collage hospital in
Roytasn Oldham, England. Both Patrick Stepate (gynecologist) and Robert
Edward (physiologist) worked together to develop the IVF technique. Stepate
described a new method of egg extraction and Edwards were carrying out a way
to fertilize egg in the lab, but the first successful ICSI birth took place in 14 th
January 1992. This technique was developed by Gianpiere D.palmoro. At the
vrije universteit Brussel in the center for reproductive medicine. Actually the
discovery was made by a mistake when a spermatozoid was put in cytoplasm.

❖ IVF over age 40:-

There will be a risk for a woman who are older and over the age of 40.
The older the woman the riskier the pregnancy. As woman get older they are
seem to suffer from conditions such as gestational diabetes and pre-eclampsia. If
older woman do this process over age 40, their offspring may be of lower birth
weight and more likely to require intensive care.

The oldest woman to give birth using IVF and egg donor was in 2004 at
the age of 66, and at September 2019 a 74-year old woman became the oldest
ever to give birth after she has delivered twins at a hospital in Guntur, Andhra
Pradesh.

*pregnancy after menopause:

IVF has allowed woman to be pregnant in

their fifties and sixties. Woman whose uteruses have

been appropriately prepared receive embryos that
originated from an egg donor. This womans won't

have a genetic with the child link but they will have

a physical link through pregnancy and childhood. In

many cases the child father genes is of the womans
partner. The uterus after menopause is fully capable of Normal vaginal canal Vs Menopause
carrying out pregnancy.
 ❖ References :-

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stimulation in IVF using ovarian reserve makers: theory to practice.
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fertilization for sub-fertile couples"(pdf).
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backing clinical decisions with scientific and clinical evidence.
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human fertilization and embryology authority.
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reducing cost and increasing safety.
• HCG injection after ovulation induction with clomiphene citrate at
Medscape. By Peter Kovacs. Posted: 23 April 2004.
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fallopian tubes: comparison between gamete intrafallobian transfer,
combined intrauterine and intraperitoneal insemination, and controlled
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Genetics.
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