assisted reproduction technology

Abdulkareem Sultan Al-Olama 1

Assisted Reproduction Technology

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Introduction Infertility is a very common condition

affecting approximately 13-14% of couples in the reproductive age group.

Although this prevalence has remained stable over the last few years, the demand for infertility services has increased substantially.

This increase is due primarily to the Baby Boom generation entering into the reproductive age group at a time of highly publicized technological advances.


Topics of Discussion

Definition of Infertility & ART Common causes of infertility Who is eligible for ART Methodology of ovulation induction Improving SPA Other techniques Counseling couple


Topics of Discussion Cont’d

Failure rate Cost effectiveness


Definition of Infertility & ART Infertility is defined classically as

the inability to conceive after 1 year of unprotected intercourse. This definition is based on the cumulative probability of pregnancy:


Definition of Infertility & ART Cont’d

Month Monthly Probability Cumulative Probability

1 0.2 0.202 0.2 0.363 0.2 0.494 0.2 0.595 0.2 0.676 0.2 0.747 0.2 0.798 0.2 0.839 0.2 0.86

10 0.2 0.8911 0.2 0.9112 0.2 0.93


Definition of Infertility & ART Cont’d

ART refers to all techniques involving direct retrieval of oocytes from the ovary

ART procedures include IVF, GIFT, ZIFT, and ICSI.

The simplest ART procedure, IVF has been around for over 20 years and is perhaps the most commonly recognized ART of all procedures.


Common causes of infertility

Causes of InfertilityCause Couples Women

Male 35% N/A

Ovulatory 15% 40%

Tubal 35% 40%

Unexplained 10% 10%

Other 5% 10%


Common causes of infertility Cont’d

Female factors Cervical factor Ovulatory factor (PCOs) Uterine factor (endometriosis) Pelvic factor



Polycystic Ovarian Syndrome (PCOS) Also known as Stein-Leventhal syndrome

Also known as hyperandrogenic chronic anovulation is a benign disorder that commonly results in infertility.

PCOS is characterized by irregular ovulation and menses, obesity, insulin resistance, acne, and hirsutism.

Most women with PCOS also have ovaries filled with multiple benign cysts.


Common causes of infertility (PCOS) Cont’d

How does PCOS contribute to Infertility? Impaired fertility is a prominent feature of

PCOS. This is believed to result from elevated

insulin levels that stimulate excess androgen production by the ovaries.

The androgens cause premature follicular wasting which causes inconsistent or absent ovulation, which is associated with infertility.


Common causes of infertility (PCOS) Cont’d1. Symptoms

Irregular or absent periods Lack of ovulation Weight gain Hirsutism (excessive hair growth) Insulin resistance Acne Male-pattern balding Multiple small ovarian cysts-these may be

seen by an ultrasound examination Ancthosis nigrans (darkening of the skin at

the nape of the neck and under the arms and breasts).

Diagnosis:


2. Blood Work/Hormonal Testing: Laboratory testing is important for

diagnosis but it is crucial to look at multiple values collectively.


Diagnosis:


3. Ultrasound: Ultrasound of the pelvis is typically

performed when the clinician suspects PCOS.

If >10 cysts are found in either ovary that are less than 10mm, this meets the ultrasound criteria for PCOS. Furthermore, polycystic ovaries are typically 1.5 to 3 times the normal size.

Just the presence of polycystic ovaries, without symptoms and/or consistent blood work, does not confirm a diagnosis of PCOS.


Diagnosis:


Treatment Weight Loss, Progestins, Oral

Contraceptives, Anti-Androgens, GnRH agonists, Fertility drugs, Surgical therapy:

a) Ovarian wedge resection b) Laparoscopic ovarian drilling



Endometriosis Endometriosis can be defined as a

nonmalignant disorder in which functioning endometrial tissue is present outside the uterus.

The incidence of this disease ranges from 10-15% in women between the ages of 25 and 44 who are actively menstruating, but it also occurs in teenagers.

It is estimated that 25-50% of infertile women have this disease.



The incidence is higher in first degree relatives of women with endometriosis, which suggests that heredity may play a role.

In addition, there is also a higher prevalence of the disease in women who delay childbearing or who are of Asian descent.

Common causes of infertility (Endometriosis) Cont’d


Causes and Symptoms The cause of endometriosis is unknown,

however there are several theories. The first theory is known as retrograde

menstruation, or the movement of sloughed endometrial tissue back through the fallopian tubes and into the abdominal cavity. This tissue can then attach itself to various internal organs or tissues outside of the uterus.

Immune system dysfunction. It is believed that certain women may develop endometriosis due to deficiencies in their immune system.



In women without endometriosis, the immune system destroys any ectopic implants that may develop. However, in women with endometriosis, there is an altered immune response and the body is unable to destroy the growth of the implants.

Furthermore, some scientists believe that endometriosis is an autoimmune disorder. This means that the body makes antibodies to endometrial cells. These antibodies may destroy the healthy endometrium found in the uterus, but are ineffective in destroying ectopic implants.



Symptoms Pelvic pain and cramping before

and during periods Pain during intercourse Inability to conceive Fatigue Painful urination during periods Gastrointestinal symptoms such as

diarrhea, constipation, and nausea



There are other medical conditions that have similar symptoms and should be considered prior to making a diagnosis of endometriosis. Conditions that may cause generalized pelvic pain include:

Pelvic inflammatory disease (PID) Pelvic adhesions Neoplasms (cancers), both benign or

malignant Ovarian torsion Sexual or physical abuse Other causes that are not gynecologic in

nature



How does endometriosis contribute to infertility? The cause of infertility is believed to

result from the scarring and adhesions that form in the reproductive tract as a result of inflammation.

Scar tissue and adhesions may reduce fertility by either obstructing or distorting the shape of the fallopian tubes, which in turn impedes the passage of sperm to the egg.



In the event that sperm do reach the egg, they may encounter a hostile environment unfavorable to fertilization.

Finally, scarring from endometriosis may obstruct the fallopian tubes so that if an egg is fertilized, it may be unable to travel to the uterus for implantation.



Diagnosis One of two techniques may be used to

confirm the diagnosis of endometriosis. Both procedures involve visualization of the pelvic cavity in order to confirm the presence or absence of ectopic implants.

laparoscopy laparotomy

If there are any suspected ectopic implants, they are biopsied in order to determine the presence of endometrial cells.



Who is eligible for ART Women with tubal diseases Unexplained infertility Endometriosis Immunologic causes for infertility Women with premature ovarian

failure Individuals with male factor infertility

(e.g., abnormalities in sperm production, function or transport or prior vasectomy)


Methodology of ovulation induction Cont’d

Basically, this term refers to the use of medications to stimulate your body to produce one or more eggs.

Ovulation induction can be as simple as taking a daily pill or more complicated, like injecting fertility medications and seeing your specialist daily for necessary monitoring. The simplest form of ovulation induction involves taking clomiphene.


More potent medications, known as the gonadotropins, are available for more intensive ovulation induction.

Gonadotropins are injectable medications that are made up of a combination of follicle stimulating hormone (FSH) and luteinizing hormone (LH) or just FSH alone.

These hormones can be very helpful in getting a woman to produce and release her eggs.

Methodology of ovulation induction Cont’d


The success of ovulation induction in achieving a pregnancy is highly variable. It depends on the diagnosis, age, the medication being used, and numerous other factors.

Methodology of ovulation induction


Improving SPA

Sperm penetration assay (SPA) is a multi-step laboratory test that offers a biological assessment of human sperm fertilizing ability.


ZIFT GIFT TEST POST ICSI TESE MESA

Other techniques


Other techniques Cont’d

ZIFT Zygote Intrafallopian Transfer. ZIFT may

be recommended if the husband has severe male fertility factor or if there has been difficulty confirming fertilization with past procedures. ZIFT has the advantages of allowing fertilization to be confirmed and it has demonstrated higher success rates than IVF when used for the appropriate indications.

One disadvantage with ZIFT is that the transfer of the zygote must be performed through a laparoscope.


GIFT Gamete intrafallopian transfer was

developing in 1984 as a variation of in vitro fertilization (IVF).

Gift is recommended when unexplained infertility infertility due to immunological factors endometriosis selected cases of male infertility Tubal infertility

A requirement for the procedure is that the female partner having at least one open (patent) fallopian tube.



TEST Tubal Embryo Transfer; the

placing of cleaving embryos into the fallopian tube.

POST Peritoneal Oocyte and Sperm

Transfer; the placement of oocytes and sperm into the pelvic cavity



ICSI Intracytoplasmic sperm injection, or ICSI,

was developed to treat couples who previously had a very poor probability of achieving fertilization due to the male partner's extremely low numbers of viable sperm.

This treatment, when combined with in vitro fertilization, allows these couples a more favorable probability of achieving conception.



TESE Testicular Sperm Extraction

MESA Microsurgical Epididymal Sperm

Aspiration



Counseling couple

The use of skills that enable a client to recognize and identify his (sic) own problems, and the ability to help client find his own solution or resolution.

The Human Fertilization and Embryology Authority (HFEA) state in their code of practice that three sorts of counseling must be available at licensed treatment center. These are: Support counseling Implications counseling Therapeutic counseling


Success rates "take home baby rate" One of the first questions that most

people ask is "what is the chance for success?" The best estimate is that the birth of a live baby occurs in approximately 15-25% of women in whom embryos are transferred into the uterus.

The 1998 nationwide live birth rate as reported in the IVF-ET Registry, was 24.9%.

The corresponding rate for 1989 was 14%.


Success varies with many factors, including the number of embryos that are transferred.

If one embryo is transferred, there is approximately a 7% chance of successful implantation; with two embryos, the success rate increases to 18%.

The rate peaks with the transfer of three to four embryos. Presently, the collection of oocytes, fertilization, and early embryo growth are accomplished with a high degree of efficiency.

Success rates Cont’d


The major hurdles to success are implantation after embryo transfer and early pregnancy loss. The rate of early pregnancy loss is slightly, but not significantly, higher with ART compared to spontaneous conception.

The risk of early pregnancy loss increases with age of the female partner. Over age 40, ART success rates decline dramatically.

Pregnancy complications tend to be higher with ART pregnancies, primarily because of the much higher rate of multiple pregnancy.



Twins occur in about 25% of ART pregnancies versus 1-2%of spontaneous pregnancies. The risk of more than a twin pregnancy is less than 5%.

To put these figures into perspective, studies have shown that the rate of pregnancy in couples with proven fertility in the past is approximately 20% per cycle. Therefore, although a figure of 15-25% may sound low, it is equal to or greater than the chance that a fertile couple will conceive in any given cycle.



Cost effectiveness

assisted reproduction technology

Education

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common conditionaffecting

adiagnosis of pcos

associatedwith infertility

infertility services