IMLE Preparatory Course

Lecture 63
Obstetrics and Gynecology
Assisted Reproductive Technology
Assisted reproductive technologies
 Assisted reproductive technologies (ART) include
many techniques that allow gamete manipulation
outside the body, and have evolved greatly over
the past two decades.

 Involve surgically removing eggs from women

and combining them with sperm in the
laboratory.
Infertility
DEFINITION:
 The inability to conceive after 12 months of unprotected
sexual intercourse.
 Affects 15% of couples.
TYPES
 Primary infertility: Infertility in the absence of previous
pregnancy.
 Secondary infertility: Infertility after previous
pregnancy.
 Infertility Is a Common Problem
 The number of infertility cases has grown
exponentially in recent years
 Infertility is a complex problem and has many causes,
including physical and physiological problems with
gamete formation and hormonal imbalances
 Female factors account for 40–50% of infertile
couples.
 Male factors account for 23% of infertile couples.
 In 40% of infertile couples, there are multiple
causes.
Why the increase in infertility?

 Delayed marriage and child-bearing

 Sexually transmitted diseases
 Hormonal contraception
 Abortion
 Obesity
 Environmental Pollution
 Most importantly, IDIOPATHIC
The major causes of female infertility

- Multifactorial: 40%.
- Unexplained: 28%.
- Anovulation: 18%.
- Tubal disease: 14%.
- Endometriosis: 9%.
The Major Causes of Male Infertility
Infertility Increases with Age
Assisted Reproductive Technologies
(ART) Expand Childbearing Options
Definition
 Directly retrieving eggs from ovary followed by manipulation
and replacement. Generally employed for inadequate
spermatogenesis. Aside from intrauterine insemination,
ARTs can utilize patient or donor egg and/or sperm.
• Hormones can induce ovaries to produce many
oocytes which can be collected, sorted, and
frozen for future use
• Sperm can be pooled, or retrieved through
microsurgery and frozen in sperm banks
 Methods of Assisted Reproduction
Intrauterine Insemination
 Washed sperm is injected into the uterus.
 Must have a normal tube for fertilization to take place.

In Vitro Fertilization (IVF) and Embryo Transfer

 Egg cells are fertilized by sperm outside the uterus.
 Consists of ovarian stimulation, egg retrieval, fertilization, selection, and embryo transfer into uterus.
 Success rate of IVF is about 20%.
 Expensive.

Intracytoplasmic Sperm Injection (ICSI)

 Subtype of IVF.
 Injection of spermatozoan into oocyte cytoplasm.
 Revolutionized treatment of infertility in men with severe oligospermia (low number), azoospermia
(absence of live sperm), asthenospermia (low motility), teratospermia (abnormal morphology).
 Pregnancy rate: 20% per cycle.
 Multiple pregnancy rate: 28–38%.
 Not influenced by cause of abnormal sperm.
 Can use spermatozoa from testicular biopsies.
 Expensive.
Methods of ART cont’d
Gamete Intrafallopian Transfer (GIFT)
 Egg and sperm are placed in a normal fallopian tube for fertilization.
 Success rate is about 25%.

Zygote Intrafallopian Transfer (ZIFT)

 Zygote created via fertilization in vitro and placed in fallopian tube,
where it proceeds to uterus for natural implantation.
 Success rate is about 30%.

Artificial Insemination with Donor Sperm

 Success rate is 75% in six cycles.
 Donor sperm is used for ARTs.
 IVF ↑ the chances of multiple gestation.
 ART: Assisted Reproductive Technology

 Predominantly IVF – In Vitro Fertilization

 Expensive
 Most attempts fail to produce a live birth
 Separates procreation from the marital act
 Large loss of embryos in failure to implant,
discarding embryos, pre-implantation diagnosis,
freezing, selective reduction
Types of ART
In Vitro Fertilization
The main reason that the spermatic fluid is washed/removed from
sperm cells prior to uterine injection is?

A. To prevent urine system bacteria to penetrate the uterine cavity

B. To discard white blood cells that may contain pathologic virus of
the reproductive system
C. To prevent allergen from sensitizing the local immune system
within the uterus
D. To remove prostaglandins that may contract the uterus
E. To dilute the sperm concentration so that sperm cells can spread
on the uterus & fallopian tubes
The main reason that the spermatic fluid is washed/removed from
sperm cells prior to uterine injection is?

A. To prevent urine system bacteria to penetrate the uterine cavity

B. To discard white blood cells that may contain pathologic virus of
the reproductive system
C. To prevent allergen from sensitizing the local immune system
within the uterus
D. To remove prostaglandins that may contract the uterus
E. To dilute the sperm concentration so that sperm cells can spread
on the uterus & fallopian tubes
Indications for IVF
 Male factor infertility
 Tubal disease
 Decreased ovarian reserve
 Endometriosis
 Genetic diseases with need for genetic testing of
the embryos
 Need for third-party reproduction-donor eggs or
gestational surrogate
 Unexplained infertility
A 31-year-old patient is preparing to start in vitro fertilization (IVF) because of
obstructed fallopian tubes. On hysterosalpingogram (HSG), it is noted that she
has large dilated hydrosalpinges present bilaterally. What should be your next
step?

(A) The patient should begin her IVF treatment cycle.

(B) The patient should repeat the HSG to confirm the result.
(C) The patient should not be offered the opportunity to have IVF.
(D) Bilateral salpingectomies should be done prior to starting IVF.
(E) Her hydrosalpinges should be drained via transvaginal aspiration prior to
starting IVF.
A 31-year-old patient is preparing to start in vitro fertilization (IVF) because of
obstructed fallopian tubes. On hysterosalpingogram (HSG), it is noted that she
has large dilated hydrosalpinges present bilaterally. What should be your next
step?

(A) The patient should begin her IVF treatment cycle.

(B) The patient should repeat the HSG to confirm the result.
(C) The patient should not be offered the opportunity to have IVF.
(D) Bilateral salpingectomies should be done prior to starting IVF.
(E) Her hydrosalpinges should be drained via transvaginal aspiration prior to
starting IVF.
 Recommended Number of
Embryos to Transfer
Age Number
< 35 2 (consider 1 if previous
successful IVF cycle, great
embryos, 1st IVF cycle)
35-37 2–3
38–40 3-4
>40 5
Age independent In some cases, such as previous
failed IVF cycles or unfavorable
prognosis, OK to transfer more
 Steps in IVF
 Follicle suppression
 Controlled ovarian hyperstimulation
 Aspiration of eggs from follicles
 Fertilization, incubation and selection of embryos
 Embryo transfer
 Pregnancy test
Aspiration of eggs
High quality egg
Low quality egg
Embryologist manipulating ova and sperm
Intrauterine Insemination (IUI)
 Donor sperm is placed into the uterus of an ovulating
woman. The sperm swim up the oviduct and fertilize the
egg.
 Intracytoplasmic Sperm Injection (ICSI)

 Injection of a
single sperm
into an egg.
ICSI
In which case is it mandatory to fertilize
the ovum with ICSI during IVF cycle?
A. When the ovum is from donor to decrease
infection rate
B. Ovum from a female of age more than 40y
C. Sperm source from TESA
D. Ovum underwent zona hatching
E. Sperm tested by Comet prior to fertilization
In which case is it mandatory to fertilize
the ovum with ICSI during IVF cycle?
A. When the ovum is from a donor to decrease
infection rate
B. Ovum from a female of age more than 40y
C. Sperm source from TESA (testicular sperm
aspiration)
D. Ovum underwent zona hatching
E. Sperm tested by Comet prior to fertilization
(checks for DNA damage)
High quality 3 day old embryo
Embryo Transfer
Frozen Embryos
 Embryos may be taken
from an individual and
stored for later use.
 Once ready to use, they
can be thawed and then
placed into the uterus.
 This allows a higher chance
of pregnancy.
Some Ways Gametes Can Be Combined
 1. Father is infertile. Mother is
inseminated by donor and
carries child.

Artificial Insemination The many

+ =

and Embryo Transfer

2. Mother is infertile but able to ways gametes
can be
carry child. Donor egg is
inseminated by father via IVF.
Embryo is transferred and
mother carries child.
combined in
+ = assisted
3. Mother is infertile and unable
reproduction.
to carry child. Donor of egg is
KEY inseminated by father and
carries child.
Sperm from father
+ =
Egg from mother

Baby born of mother 4. Both parents are infertile, but

mother is able to carry child.
Donor egg is inseminated by
Sperm from donor sperm donor via IVF. Embryo
is transferred and mother
carries child.
Egg from donor
Baby born of donor + =
(Surrogate)
 1. Mother is fertile but unable to conceive. Egg from mother and
sperm from father are combined in laboratory. Embryo is placed in
InVitro Fertilization mother’s uterus.
(IVF) + =
2. Mother is infertile but able to carry child. Egg from donor is
combined with sperm from father and implanted in mother.

+ =

3. Father is infertile and mother is fertile but unable to conceive.

Egg from mother is combined with sperm from donor.

+ =
4. Both parents are infertile, but mother is able to carry child. Egg
and sperm from donors are combined in laboratory (also see
number 4, column at left).

+ =

5. Mother is infertile and unable to carry child. Egg of donor is

combined with sperm from father. Embryo is transferred to
donor (also see number 3, column at left).

KEY + =
Sperm from father 6. Both parents are fertile, but mother is unable to carry child.
Egg from mother and sperm from father are combined. Embryo is
Egg from mother
transferred to donor.
Baby born of mother
+ =

Sperm from donor 7. Father is infertile. Mother is fertile but unable to carry child.
Egg from donor Egg from mother is combined with sperm from donor. Embryo is
transferred to surrogate mother.
Baby born of donor
(Surrogate) + =
IVF has Resulted in the Birth
of Millions of Children
 Gamete Intrafallopian Transfer (GIFT)

• Eggs and sperm are

collected and
implanted into the
fallopian tube.
• Fertilization occurs
here, and the embryo
moves down the
oviduct and implants in
the uterus.
 Zygote Intrafallopian Transfer (ZIFT)
• Gametes are
collected and
fertilized by in
vitro fertilization
before transfer to
the oviduct.
Complications
 Multiple gestations- Transferring more embryos does not
necessarily lead to a greater IVF success rate. A frozen
embryo is thought to have the same potential for
successful implantation of a fresh embryo.

 Ectopic and heterotopic (both extra- & intra- uterine

pregnancies occur simultaneously) pregnancies - Patients
who undergo ART procedure are at twice the risk for
having an ectopic pregnancy as the general population.
 Complications
 Preterm birth and low-birth-weight infants- These are
higher in patients undergoing IVF.

 Ovarian hyperstimulation syndrome- This syndrome is

characterized by ovarian enlargement, ascites, and
hemoconcentration. Risk factors include polycystic ovary
syndrome, multiple follicles, and high estradiol levels.

 Congenital abnormalities- In patients who have ICSI

performed, the risk of imprinting disorders may be
increased (such as Angelman's syndrome and Beckwith-
Wiedemann syndrome).
 Ethical Issues in
Reproductive Technology
 Health risks to both parents and their
offspring resulting from ART

 Use of preimplantation genetic diagnosis

to select siblings who are suitable tissue or
organ donors for other members of the
family
 Multiple births
 Multiple pregnancies with IVF (37.4%)
 Triplets or more 8.4% (4.9% of live births)
 Prematurity: Average with triplets 33 weeks; 85% survive
 Prematurity: Quadruplets average 29 weeks; 70% survive
 Fetal risks: mental/physical disabilities such as blindness,
cerebral palsy; 5% in twins, 10% in triplets, 50% in
quadruplets
 Fetal risks: death; seven times more likely to die in the first
year; 40x more likely to die in infancy
 Maternal risks: toxemia, diabetes, hemorrhage
 Family risks: depression, social isolation, divorce
Octopulet Pregnancy
Risk of Premature Birth and Increase
Health Costs Following IVF
Preimplantation Genetic Diagnosis (PGD)
 Removal and genetic analysis of a single cell
from a 3- to 5-day old embryo

 Used to select embryos free of genetic

disorders for implantation and
development

 Has been used to select embryos tissue-

matched to siblings with Fanconi anemia or
leukemia to serve as transplant donors
Diseases and Birth Defects that can be Diagnosed
by Preimplantation Genetic Diagnosis
Preimplantation Genetic Diagnosis (PGD)
 Removing a cell from a day 3 embryo
Removal of a Polar Body for
Genetic Analysis
 Selecting an ART Program
 Qualifications and experience of the clinic and its
personnel.

 Support services available

 Cost

 Success rates of that specific program