In Vitro Fertilization (IVF) involves stimulating a woman's ovaries to develop multiple eggs, retrieving the eggs and fertilizing them with sperm in a lab, then transferring the resulting embryo(s) into the uterus. Key aspects of IVF include controlled ovarian hyperstimulation using fertility medications, egg retrieval under ultrasound guidance, fertilization via intracytoplasmic sperm injection if needed, embryo culture until blastocyst stage, and embryo transfer into the uterus. Success rates of IVF depend on factors like the woman's age, cause of infertility, and embryo quality.

1. IVF
In Vitro Fertilization
Areej Abu Hanieh

2. DEFINITION
• the ovaries are stimulated by a combination of
fertility medications and then one or more
oocyte(s) are aspirated from ovarian follicles.
• These are fertilized in the laboratory ("in
vitro"), after which, one or more embryo(s)
are transferred into the uterine cavity.

3. • A reasonable course when counseling young
couples with no clear block to conception :
• is to complete a total of one year of
unprotected intercourse and one year of
conventional treatment.
• couples may be offered three to six cycles of
superovulation and intrauterine insemination
(IUI) before proceeding to IVF.

4. PATIENT SELECTION
• Fertility issues —
• How to select the patient :
• Tubal factor (IVF is primary therapy if tubes are
completely blocked).
• Severe male factor infertility (mild male factor
may be treated with inseminations; if male factor
is severe, IVF is primary therapy of choice)
• Diminished ovarian reserve (time to conception is
critical and success with other therapies is low)

5. • All other causes of infertility, after failing treatment with
less invasive therapies (eg, ovulatory dysfunction,
endometriosis, unexplained infertility)
• Ovarian failure (although donor eggs must be used in this
case)
• Uterine factor (if severe, such as Asherman syndrome or
irreparable distortion of the uterine cavity, gestational
surrogacy may be needed in conjunction with IVF)
• IVF has also been used to achieve pregnancy in gestational
carriers of women who do not have a uterus or in whom
pregnancy is medically contraindicated. (See "Surrogate
pregnancy".)
• Better to offer IVF as a primary treatment option to couples
with the female partner over 40 years of age.

6. • IVF can be useful in the following clinical settings:
• Sex selection "Techniques for preimplantation sex
selection”
• Preimplantation genetic diagnosis
• Prevention of mitochondrial disorders – Two IVF
techniques, maternal spindle transfer and pronuclear
transfer, are promising new applications of IVF for women
with inherited mutations in mitochondrial DNA (mtDNA),
which are an important cause of genetic diseases for which
there is no effective treatment.
• Potential correction of germline mutations – Gene editing
of an embryo prior to transfer has the potential to correct
heritable mutations that cause significant disease , using
CRISPER CAS 9 .

7. • Disadvantages of IVF include:
• the high cost.
• the need for procedures and drugs associated
with some risk to the woman.
• an increased rate of multiple gestation.
• possibly a slight increase in fetal
complications.

8. • Pre-cycle factors associated with success —
Several preprocedure factors can affect the
success of IVF :
• Younger maternal age — Although IVF may
largely overcome infertility in younger women,
it does not reverse the age-dependent decline
in fertility in older women, particularly those
over 40 years.

9. • PCOS , decrease rate of successful IVF .
• Endometrial preparation for frozen-thawed
embryo transfer .

10. • Adequate ovarian reserve — Serum follicle stimulating hormone
(FSH) and estradiol concentrations may help predict the success of
the IVF procedure :
• Elevated serum FSH concentrations in the early follicular phase
(cycle day three) are associated with a poor prognosis for
pregnancy after IVF .
• High day three serum estradiol concentrations are also associated
with a poor pregnancy outcome after IVF because they appear to
be associated with rapid premature follicle recruitment and
reduced oocyte numbers.
• Summary : We measure serum FSH and estradiol on cycle day 3
(third day of menstrual bleeding) in all women over the age of 35
years who are contemplating IVF, and we do not start IVF cycles in
those with serum FSH concentrations >20 mIU/mL or serum
estradiol concentrations >100 pg/mL (367 pmol/L).

11. • Factors with a negative effect on success:
• Hydrosalpinx: distally blocked fallopian tube filled
with serous or clear fluid.
• Smoking
• Altered microbiota: RNA genome studies have
reported that the uterine cavity has a unique
microbiome, with initial studies suggesting
dominance
of Bacteroides and Lactobacilli species

13. Ovarian Stimulation
• we give 4 mg single dose of leuprolide acetate
35 hours prior to retrieval or divided in 2
doses.
• Leuprolide :leutinizing hormone releasing
hormone

15. Controlled Ovarian Hyperstimulation
• As a result, multiple mature oocytes could be
retrieved and fertilized.
• regimens that include daily injections of
exogenous follicle-stimulating hormone (FSH).
• Tamoxifen and Clomiphene .

16. Suppression of spontaneous
ovulation
• When used in conjunction with (IVF), controlled ovarian
hyperstimulation confers a need to avoid spontaneous ovulation,
since oocyte retrieval of the mature egg from the fallopian
tube or uterus is much harder than from the ovarian follicle. The
main regimens to achieve ovulation suppression are:
• GnRH agonist administration given continuously before starting the
gonadotropin hyperstimulation regimen. In long protocol to inhibit
LH .
• GnRH antagonist administration, which is typically administered in
the mid-follicular phase in stimulated cycles after administration
of gonadotropins , in short protocol.

17. individualized dosing of FSH = 150 IU/day

18. Long protocol
• "Long protocols" involve starting medications in
the menstrual cycle before the IVF cycle; this can
be done with GnRH agonist .
• administered daily for about two weeks or until
down-regulation is complete.
• When stimulation begins, hMG (or FSH, or both )
is administered in a dose of 225 to
300 IU/day subcutaneously to stimulate follicular
growth, with the GnRH agonist being continued
at a lower dose to prevent a premature surge in
luteinizing hormone (LH) secretion.

19. Short protocol
• initiated at the time of spontaneous
menstruation or after several days or weeks of
oral contraceptive pills.
• One such regimen uses a low-dose of leuprolide,
40 mcg twice daily, started on day 3 of bleeding
or three to five days after the last oral
contraceptive pill.
• Leuprolide :leutinizing hormone releasing
hormone

20. FOLLICLE ASPIRATION AND
FERTILIZATION
• Oocyte retrieval : It is performed 34 to 36
hours after hCG administration. Under direct
ultrasonographic visualization and some type
of analgesia/anesthesia.
• Number of oocytes retrieved : up to 15 egg .

21. In vitro fertilization
During in vitro fertilization,
eggs are removed from
mature follicles within an
ovary (A). An egg is
fertilized by injecting a
single sperm into the egg
or mixing the egg with
sperm in a petri dish (B).
The fertilized egg (embryo)
is transferred into the
uterus (C).

22. Egg retrieval technique
Typically, transvaginal ultrasound aspiration is used to retrieve eggs.
During this procedure, an ultrasound probe is inserted into vagina to
identify follicles, and a needle is guided through the vagina and into
the follicles. The eggs are removed from the follicles through the
needle, which is connected to a suction device.

23. Fertilization
• Insemination. During insemination, healthy
sperm and mature eggs are mixed and incubated
overnight.
• Intracytoplasmic sperm injection (ICSI). In ICSI, a
single healthy sperm is injected directly into each
mature egg. ICSI is often used when semen
quality or number is a problem or if fertilization
attempts during prior IVF cycles failed.

24. ICSI
In intracytoplasmic sperm injection (ICSI), a single healthy sperm is injected
directly into each mature egg. ICSI is often used when semen quality or
number is a problem or if fertilization attempts during prior in vitro
fertilization cycles failed.

25. Blastocyte
Three days after fertilization, a
normally developing embryo will
contain about six to 10 cells. By
the fifth or sixth day, the fertilized
egg is known as a blastocyst — a
rapidly dividing ball of cells. The
inner group of cells will become
the embryo. The outer group will
become the cells that nourish and
protect it.

26. Management
• Briefly, fertilization of the oocyte is confirmed by
observing two pronuclei within the zygote about 17
hours after insemination or ICSI. After fertilization, the
individual cells of each embryo ("blastomeres") divide
every 12 to 14 hours, so that the embryo reaches
approximately 8 cells by 72 hours after egg retrieval.
Embryos between days 2 and 4 are called "cleavage
stage embryos." The blastocyst stage is reached by
about day 5 after retrieval, and implantation is
expected by day 7 after egg retrieval, so transfer should
take place prior to this time.

27. • Embryo transfer — embryos are maintained in culture
for a variable period of time prior to transfer:
• Cleavage stage: Most programs transfer embryos to the
uterus about 72 hours after egg retrieval (four to eight
cell, cleavage stage) .
• Blastocyst stage: Day 5 transfer (blastocyst stage) is the
next most common time for transfer . Major
advantages of blastocyst stage transfer are the ability
to perform PGD and the large reduction in multiple
gestation with single blastocyst transfer.
• PGD : Preimplantation genetic diagnosis

28. Certain procedures before implanting
• Assisted hatching. About five to six days after
fertilization, an embryo "hatches" from its surrounding
membrane (zona pellucida), In older women, and
multiple failed IVF attempts, doctor recommend
assisted hatching — a technique in which a hole is
made in the zona pellucida just before transfer to help
the embryo hatch and implant.
• Preimplantation genetic testing. Embryos are allowed
to develop in the incubator until they reach a stage
where a small sample can be removed and tested for
specific genetic diseases or the correct number of
chromosomes, typically after five to six days of
development.

29. • Luteal phase support — plays a major role in the
success or failure of embryo implantation after
IVF .
• To optimize endometrial receptivity, it is common
practice to administer
a progesterone supplement during the luteal
phase .
• Progesterone supplementation is generally
initiated on the day of oocyte retrieval or at the
time of embryo transfer.

30. Risks
• Multiple births.
• Premature delivery and low birth weight.
• Ovarian hyperstimulation syndrome. Use of injectable
fertility drugs, such as human chorionic gonadotropin
(HCG), to induce ovulation can cause ovarian
hyperstimulation syndrome, in which your ovaries become
swollen and painful. The drugs to treat this will be
mentioned .
• Miscarriage. by using of frozen embryos during IVF
• Egg-retrieval procedure complications. Use of an aspirating
needle to collect eggs could possibly cause bleeding,
infection or damage to the bowel, bladder or a blood
vessel.
• Ectopic pregnancy

31. Follow up
• Better to decrease physical activity after
implantation .
• Monitoring for pregnancy .
• Over hyperstimulation syndrome .

32. Reasons for failure
Poor endometrial receptivity:
• Poor endometrial development (thin
endometrium, altered expression of adhesive
molecules)
• Uterine abnormalities (submucosal myomas,
uterine septum)
• Hostile environment (hydrosalpinges,
infection)

33. Poor embryo transfer efficiency:
• Traumatic embryo transfer (eg, use of rigid
transfer catheters)
• Inaccurate placement of the embryos (eg, lack
of ultrasound guidance)

34. • References :
• Up to date
• Mayoclinic