In Vitro Fertilization (IVF)

In Vitro Fertilization (IVF)
IVF involves fertilization outside the body in an artificial environment. This procedure was first used for infertility in humans in 1978 at Baurne Hall in Cambridge, England. To date millions of babies have been delivered worldwide as a result of IVF treatment. Over the years the procedures to achieve IVF pregnancies have become increasingly simpler, safer and more successful. There are times when it is difficult or impossible for the sperm and egg to meet in the fallopian. IVF offers an opportunity to avoid such problems by allowing fertilization to occur outside the body in a glass dish; hence the use of the latin words “ïn vitro’’ which literally means ‘’in glass’’ and the baby named as ‘’test tube baby’’.

What types of fertility problems might be helped by IVF?

  • Absent fallopian tubes or severely damaged tubes or bilateral tubal blockage that cannot be treated successfully by surgery.
  • Endometriosis that has not responded to surgical or medical treatment.
  • A male factor contributing to infertility, in which sperm counts or motility are low but there are enough active sperms  to allow fertilization in the laboratory.
  • Unexplained infertility that has not responded to other treatments.
  • Infertility secondary to sperm antibodies.
  • Pelvic adhesions.
  • Chronic anovulation where needs lots of drugs for getting mature eggs.

Our IVF/ICSI co-ordinator discusses in depth with the couple about the procedure, risk involved, cost and success of the treatment.
Prior to becoming eligible for treatment in an IVF cycle couple will need to complete the tests recommended by physician, have to have current infectious disease testing (good for 1 year), and  consent forms must be signed and returned before starting each cycle.

Process

Treatment involves several steps

  • Down regulation which temporarily switches off the pituitary.
  • Stimulation of the ovary to produce several fertilizable oocytes (eggs).
  • Monitoring by ultrasound.
  • Retrieval of the oocytes and culture of the embryos in the laboratory.
  • Placement of the embryos into the uterus for implantation (Embryo transfer or ET)

Step 1: Down regulaton:
It is done to stop the function of the pituitary gland so it can not interfere the artificial treatment cycle. It starts on D2 or D21 of regular or progesterone withdrawal cycle. Inj suprefact (GnRHa) .5ml sc daily is given in long protocol for 14 days. It takes 2-3 weeks for complete down regulation. It is tested by doing USG and observing the endometrial and ovarian status. Emdometrium becomes thin and ovaries become acystic. Sometimes blood testing for E2 and LH is needed.

Step 2: Stimulation:
Once down regulation achieved injection gonadotropin is given to produce multiple eggs. Dose of gonadotropin is fixed according to patients’ age and ovarian reserve. It takes 10-12 days stimulation to get mature eggs. Regular ultrasonographic monitoring is done to see the recruitment and development of eggs and to adjust the dose of gonadotropin according to response of the patient. Development of 10-12 follicles is optimum. Monitoring also needed to avoid ovarian hyperstimulation syndrome ( development of too many follicles). When follicles attain the size of 18 mm or more ( at least 3 follilces) ovulation is triggered by  giving  injection hCG. Ovum pick up is scheduled 36 hours after hCG injection.

Step 3: Egg retrieval and culture
On the day of the retrieval we will need a semen specimen which needs to be collected at the clinic.  A collection room is available for privacy. Those who get nervous can provide sample beforehand at their convenient time. Sample is kept freeze for future use on the day of procedure. Female partner will come in empty stomach as G/A may needed. Patient needs to come at least 30 minutes before retrieval. The retrieval procedure takes approximately 10-15 minutes and patient can go to recovery room within 30 minutes. The procedure involves a transvaginal ultrasound with a needle guide that is used to aspirate the fluid from within the follicles under real time visualization. The oocytes are identified in the follicular fluid by an embryologist. The number of eggs will be known shortly after the completion of the procedure.

The recovery usually takes less than 30 minutes. Patient will be given discharge instructions by medical officer. Patients are allowed to call medical officer further clarification if needed. The next day fertilization is checked and result is informed to the patient. 100% of the oocytes retrieved are not usually fertilized. There is no good way to predict how many eggs will actually fertilize.

High quality egg at IVF

Mature egg

Step 4: Embryo transfer

Depending on several factors, including number of fertilized eggs and age, the embryos will be transferred into the uterus on either day 2, 3 or at the blastocyst stage (5-6). Egg retrieval day is considered day 0.


               Eight cells grade 1 embryo

Eight cells grade I embryo Eight cells grade 1 embryo

Supplemental progesterone will be administered following the retrieval. Dosing instructions is given along with discharge instructions prior to leaving on the day of retrieval. Progesterone is usually continued until approximately 10-12 weeks into the pregnancy until the placenta has completely taken over the hormone production function.
A pregnancy test will be done 15 days following the embryo transfer. Sometimes it is done earlier if there is complains of spotting. This test should be done even if per vaginal bleeding occurs since there is still a good possibility of an ongoing pregnancy.

Cancellation:

There are times when cycles will need to be canceled. One of the possibilities for cancellation of a cycle is lack of adequate ovarian response. If there is no good number of follicles it is better served by attempting pregnancy by timed intercourse or intrauterine insemination (if tubes are patent and semen parameter is suitable). For some patients this saves financial resources for future attempts at IVF where the follicular response may be improved. There are a good number of pregnancies that have resulted from “canceled” cycles. Other reasons of cancellation of cycle is ovarian hyperstimulation syndrome ( where too many eggs are developed and causes complications).

Monitoring:

Ultrasounds gives an estimate of the numbers of follicles. It is important to remember the number of oocytes retrieved is not always the same as the number of follicles seen on ultrasound. Sometimes there are very few oocytes retrieved when the number of follicles looks encouraging. There is always a possibility that no oocytes fertilize or no embryos survive to the day of transfer. Obviously if this occurs the embryo transfer would be cancelled.

Intracytoplasmic sperm injection (ICSI)
Male-factor infertility occurs in approximately 40% of couples who are unable to achieve a pregnancy. Severe male-factor infertility accounts for 25% of infertility. Less than 10% of male infertility can be successfully treated with surgical or medical therapies. Fortunately, there are some other therapies for the remaining 90% of couples desiring pregnancy. Some will be helped by superovulation of female partner with drugs such as Gonal-F, Puregon and Menogon along with intrauterine insemination. Most couples will be better served by in vitro fertilization (IVF) combined with intracytoplasmic sperm injection (ICSI).

ICSI is indicated when there are not enough normal, motile sperm for intrauterine insemination or standard IVF. It is also used frequently when there are poor fertilization results in previous IVF cycles. It is a micromanipulation technique originally developed in Belgium. By using a powerful microscope we are able to isolate a single sperm, aspirate it into an extremely thin glass pipette and inject it into a single egg. This technique does not require large numbers of motile sperm and bypasses the need for the sperm to penetrate the egg by itself. With the help of ICSI, fertilization is achieved and embryos that continue to divide are ready for transfer into the uterus in several days. No increase in congenital anomalies (birth defects) have thus far been observed with ICSI.

Candidates for ICSI:
Male

  • Insufficient number of available sperms or severe oligopsermia
  • Insufficient number of normal sperms or teratospermia
  • Low grade sperm motility or asthnospemia
  • Azoospemia both obstructive and non obstructive.
  • Anti-sperm antibodies
  • Failure of fertilization due to sperm function defect

Female

  • Resistant zona pellucida
  • Anti-sperm antibodies
  • Failure of fertilization in conventional IVF

As far as the patient is concerned, the procedure is exactly similar as that of IVF. Acquisition of sperm and subsequent laboratory technique is different for ICSI. Sperm can be provided by the husband in the form of semen or acquired through operation. Surgical aspiration of sperms is carried out by a fine needle attached to a syringe which is pushed into the tube carrying sperms from testis to the penis or a piece of testicular tissue is obtained surgically and processed in the laboratory to release entrapped mature sperms.
Individual mature sperm is then picked with a very fine needle through a very elaborate equipment and injected into the egg which is collected in the similar manner as IVF. The rest of the procedure is similar as IVF.
From prepared embryos some are transferred to uterus and rest are cryopreserved for future use.

             
ICSI Station

                                    Intracytoplasmic sperm injection (ICSI)   

Cryopreservation:

In the event there are more embryos surviving than are needed at the time of transfer surplus embryos are frozen, or cryopreserved, for later transfer. The frozen embryo transfer (FET) process does not involve taking injectable gonadotropins. Coordinating the frozen embryo transfer can be done with or without medications. Cryopreservation allows for attempts at achieving pregnancy without the high-cost of a repeat IVF cycle.

Assisted Hatching:
It is a technique involving the removal of a small portion of the zona pellucida (outer layer of the oocyte or early embryo). This process is done prior to transfer. Age is the predominant determining factor for using assisted hatching. Assisted hatching is considered on an individual basis.

Risks:
There are multiple risks involved with the medications and retrieval process. A brief summary is provided here. Patient should have a full understanding of these risks and ask questions regarding these risks prior to signing the consent forms.

Ovarian Hyperstimulation Syndrome(OHSS):
This is a combination of symptoms that result from the elevated levels of hormones and other factors that result from excessive stimulation of the ovaries. It can be predicted beforehand and can be prevented by adopting a number of strategies. In spite of preventing measures severe symptoms like ascitis, respiratory distress and other complications may develop. In that event cycle is cancelled, embryo transfer is deferred and kept frozen. Sometimes in severe cases ICU support may needed.

Multiple gestations:
The use of medications to stimulate increased numbers of follicles will also increase the rate of multiple pregnancies. Up to 20 percent of pregnancies conceived while taking gonadotropins will be multiple gestations. Most of these will be twins, however, triplets and higher numbers of gestations are seen as well. This is in contrast to the one to two percent risk of multiple gestations in the general population.

Ectopic pregnancies (tubal):
There is a very small increase in the incidence of ectopic pregnancies due to gonadotropins. The risk of ectopic pregnancy is not eliminated by IVF, though it is very uncommon.

Ovarian torsion:
With ovarian stimulation from gonadotropins., the size of ovaries is increased. This increase in size can lead to a twisting of the ovaries which interrupts the blood supply. Surgery is often required to alleviate the problem. Torsion occurs in less than 1% of patients.

Ovarian cancer:
There is much debate about relation of ovulation inducing agents with a woman’s risk for ovarian cancer. The risk of ovarian cancer does have a correlation with the number of times a woman ovulates. Pregnancy and breast feeding has been shown to decrease the risk of breast cancer as do birth control pills.

Infection:
The retrieval process involves the passage of a needle into the abdominal cavity through the vagina. There is a risk of infection as a result of the oocyte retrieval. Prophylactic antibiotics are used to help prevent infections. The actual incidence of peritonitis is exceedingly rare.

Perforation and haemorrhage:
Injury to intra-abdominal organs and vessels is always a concern during the retrieval process. Organs at risk include the bowel, bladder, and vessels. Because the needle is relatively small this complication is not as common as one would expect. Keep in mind needles are used to puncture vessels in order to draw blood. Punctures of intra-abdominal organs likely seal themselves in a similar fashion.
Following the procedure someone may experience a moderate amount of abdominal discomfort due to enlarged ovaries and manipulation from the procedure.

Chancess of success:
The success of IVF/ICSI depends on several factors but the most important are the woman’s
age and the quality of sperm.The result tend to be better in younger women. It is around 30% for women aged 30, but only 10% at the age of 40 and 6% after 40 years. The effect age appears to be due to a combination of factors like

  • A reduced response to the drugs that stimulates the ovaries.
  • A smaller of implantation of embryos.
  • A higher rate of miscarriage

Repeated attempt increases the success.

Effects on the baby:

Babies born as a result of IVF/ICSI have been studied closely for many years because of an understandable concern about their development into healthy children. Evidences suggest that the number of abnormalities found in ART babies are not more than that conceived naturally. Only difference is that patients get pregnant at their later age and age related abnormality may be higher in these groups.

Islamic point of view:

In Islamic point of view it is permissible by modern Islamic scholars when procedure is done by gametes from husband and wife. Third parties involvement is not permissible in Islam.