In the month prior to the IVF stimulation cycle, medications/injections are given to suppress the body’s natural hormones so that the subsequent stimulation of ovaries is better controlled.
You may be put on birth control pills in this cycle. This may seem strange – you are trying to get pregnant and we are putting you on birth control pills. Actually, though, using birth control pills before a treatment cycle has been shown to decrease your risk of ovarian hyperstimulation syndrome (OHSS) and ovarian cysts and hence may improve the chances of success. It also causes suppression of LH hormone and suppression of the entire cohort of follicles so that all the follicles are in the same phase and will grow simultaneously.
Another possible option is that we monitor your follicular growth and ovulation and give you estradiol valerate tablets till you get your periods. This is to suppress the FSH hormone in your body which helps in follicle recruitment. If the body’s FSH is suppressed, we can recruit more number of follicles by giving injections. Suppression of FSH does not allow the natural selection of the follicle by the body, thereby uniform recruitment of the follicles and we will get more number of follicles.
Sometimes we monitor your follicular growth and ovulation and start Injection Lupride. This is used in the long protocol of IVF and the basic aim is the same – to suppress the body’s natural hormones so that all the follicles (cohort) are maintained at the same size and can grow equally.
The type of protocol differs from patient to patient, depending on their age, previous response, endometrial lining etc.
Generally the husband is told to give one semen sample before the start of the cycle. This sample will be frozen till the day of actual oocyte retrieval. This is because the stress of the day and anxiety can make it difficult for some to give the semen sample on the day of oocyte retrieval. So just in case that happens, we will have a backup sample.
Oocyte retrieval as well as embryo transfer takes place through the vaginal route. Therefore if there is any vaginal infection, it may be transmitted to the ovaries or the uterus. This may hamper the results of IVF. Even infection in the male genital tract can affect the results and more important, can be a source of transmission to the female partner. Treating genital tract infection is very important. Therefore, we give a course of oral antibiotics to both the husband and wife inorder to clear the genital tract of any infection. In addition,vaginal pessaries (combination of antibiotic and antifungal preparation) are given to clear the vaginal tract of any infection.
This is when we actually start the IVF/ICSI cycle. You will need to come on day1/day2 of periods. A baseline ultrasound is performed to rule out ovarian cysts. If a cyst is present, the cycle may be postponed to next month or the cyst can be aspirated and the cycle can be started.
If required, baseline hormone levels like Serum E2 and LH are tested. This is to make sure your ovaries are “sleeping” or are suppressed so that the stimulation of ovaries with (Gonadotrophins) HMG /FSH injections will happen correctly.
Should the results be favorable the ovarian stimulation is started.
PRINCIPLE – In a natural cycle, a woman’s ovaries will generally produce one egg. But when we are doing an invasive procedure like IVF/ICSI it is better to have more eggs which will maximize the chances of success. Also, not all stimulated follicles are mature and give eggs. In addition there is a limited rate of fertilization(all the eggs that are obtained do not fertilize). What would we do if a single egg we obtain does not fertilize? If we have more eggs, we can make more embryos and select the best embryos for transfer.
Hence injections are given to obtain controlled ovarian stimulation (COS).
Ovarian stimulation is achieved by daily injections of gonadotropins, which are given subcutaneously and can be self administered. We teach you how to take injections and 99% patients take them on their own without any problems. This helps you to cut down on hospital visits or running to your family doctor daily just to take the injections which wastes lots of time and creates unnecessary anxiety.
The stimulation process is monitored by serial ultrasounds and blood tests, which are done as and when required. The first ultrasound is generally done on the 4th /5th day of stimulation. This helps us to monitor the growth of your follicles and assess whether the dose of the injections needs to be increased, decreased or remain the same. The next ultrasound is 2 days later and then it is generally on alternate days or daily till the follicles are ready (approximately 18 to 20mm in size on USG). Transvaginal ultrasound not only helps to monitor the follicular growth but also helps to monitor the endometrial thickness.
These injections generally continue till the follicles are ready which is usually for 8 or 9 days. This comes to around 9th -11th day of periods.
When the follicles in the ovaries are ready (18-20mm) HCG injection is given for oocyte maturation. Timing this injection is vital. If it is given too early, the eggs will not have mature enough. If given too late, the eggs may be “too old” and won’t fertilize properly. The frequent ultrasounds are meant to time this trigger shot just right. Usually, the HCG injection is given when three or more follicles have grown to 17 to 19mm in size.
This is a minor surgical procedure that is performed on day care basis.
The egg retrieval takes place between 34 to 36 hours after you receive the HCG shot. It’s normal to be nervous about the procedure, but most women go through it without much trouble or pain.
You have to be fasting from midnight of the previous day of oocyte retrieval. On the day of oocyte retrieval, you have to come fasting (no tea, water etc). However, if you are taking any regular medications like that for thyroid, blood pressure, diabetes etc. you will take them in the morning with a sip of water (after confirming with us). When you come in, you will be taken in the ultrasound room for a sonography and your husband will be sent to make admission papers. After the sonography, you will be taken to the recovery room where you will be given a OT changes (operation theatre gown). An IV line will be inserted and that is the only pain you will get! You and your husband will be given consent forms to sign. You will be taken to the operation theatre.
The oocyte retrieval is done under general anesthesia with ultrasound guidance.Before the retrieval, an anaesthesiologist will give you some medication intravenously to help you feel relaxed and pain free. You are given general anaesthesia so that you will sleep completely for the entire procedure and will come to know nothing about the procedure. There is no intubation required. The whole procedure of oocyte retrieval usually takes about 15 to 20 minutes. The entire procedure is absolutely pain free.
Once the medications take their effect, a transvaginal ultrasound is used to guide a needle through the back wall of your vagina, up to your ovaries.The needle is used to aspirate the follicle, and gently suck the fluid and oocyte from the follicle in to the needle. One follicle generally contains one egg. But all the follicles do not contain an egg. On an average when we aspirate, we get one egg for every 2 follicles we aspirate. These oocytes once aspirated will be transferred to the embryology lab for confirmation of the number of eggs retrieved and further fertilization.
Video of ovum pick up
The number of oocytes retrieved varies but can usually be estimated before retrieval via ultrasound. The average number of oocytes is 5 to 10.
After the retrieval procedure, you’ll be taken to the recovery room where you will sleep off under the effect of anaesthesia for a couple of hours. Light spotting is common, as well as lower abdominal cramping, but most feel comfortable by the same evening. Once you get up you will be given a light snack. We will give you further instructions and you are ready to go home. Usually the procedure is done in the morning and you are ready to go home by afternoon or evening.
The follicles that were aspirated will be searched for oocytes, or eggs. Not every follicle will contain an oocyte.
Fig:Unfertilized immature eggs
Once the oocytes are found, they’ll be evaluated by the embryologist. If the eggs are overly mature, fertilization may not be successful. If they are not mature enough, the embryology lab may be able to stimulate them to maturity in the lab. This is called in vitro maturation which takes around 24 hours.
Fig Mature egg
Fig Vacuolated oocyte
All the oocytes which are retrieved are carefully identified and kept in the CO2 incubator. During this period the semen sample is obtained from the husband and semen processing is done which isolates the healthiest sperms. The union of male gamete(sperm) and female gamete(ovum) is known as fertilization. In an IVF laboratory, fertilization is done either through IVF or ICSI.
In an IVF, the embryologist places about 10,000 sperms in a culture dish with one oocyte.
With ICSI, which we generally prefer, the embryologist will choose a healthy-looking sperm and inseminate the oocyte with the sperm using a special thin needle.
Fig of ICSI procedure:
The culture dishes are kept in a special incubator under special conditions (specified temperature and CO2 concentration) and after 24 hours, they are inspected for signs of fertilization.
The fertilization rate with ICSI is higher than IVF. With ICSI, around 75 – 80% of the oocytes will get fertilized.
VIDEO OF EMBRYO DEVELOPMENT AFTER ICSI PROCEDURE.
The above video shows the procedure of ICSI , wherein a sperm is injected into the egg. This is followed by fertilization and formation of the embryo. It further shows the development of the embryo from one cell to 2 cell, 4 cell, morula stage and later delevoping into a Blastocyst (Day 5 Embryo)
Fig . Normal fertilization, 2 pronulclei (PN) seen
Fig. Abnormal Fertilization , 3 Pronuclei (PN) seen after 17 -18 hours
Fig . Day 2 embryo, 2 cells seen (between 36 -48 hours)
Fig . Day 2 embryos, 4 cell seen after completion of 48 hours
About three to five days after the retrieval, the fertilized eggs will be transferred. The embryo transfer is a simple procedure just like an IUI procedure. When the embryos are transferred on day 3, the embryo is said to be 8 cell stage.
Video of USG guided Embryo transfer
Above video shows the procedure of transfer of Embryo under USG guidance.
Fig 10. Day 4 embryos, cluster of 16 cells called as morula
When the embryos are transferred on day 5, it is at blastocyst stage. This is the highest form of human life that can be sustained in the laboratory.
Fig 11. Day 5 embryo, Blastocyst stage
Fig 12. Day 7 embryo, Hatched blastocyst
The number of embryos transferred will depend on the quality of the embryos and your previous discussion with the doctor.
Poor quality fragmented Embryos:
Depending on your age, anywhere from one to three embryos may be transferred. Recent studies have shown success with just one embryo transferred. The transfer will be done on a full bladder in the operation theatre. No fasting or special preparation is required for embryo transfer.
Embryo transfer does not require anaesthesia and is done on a day care basis. When you come to the IVF clinic in the morning, a routine vaginal scan is done to assess the endometrium. Then you will proceed to the recovery room, where the nurse will give you a progesterone injection. This will help in relaxing the uterus as well as maintaining good progesterone levels. You will lie down in the recovery room till your bladder is full. When the bladder is full, we take you to the operation theatre. There is soothing music which will help you to relax and be in a more positive frame of mind. At the time of transfer, the private parts will be cleaned with warm water and then the external catheter will be passed just beyond the internal os.
The embryologist will then bring the internal catheter loaded with embryos. The selected embryos are transferred into the uterus by a specially designed catheter under ultrasound guidance, which helps to transfer the embryos in correct place in the uterus i.e. 1-1.5 cms below the fundus which in turn increases pregnancy rates by up to 5-10%. After the transfer, you will lie down in the operation theatre for 10-15 minutes after which you will get up and go walking to the washroom and then lie down in the recovery room.
Video of Embryo Transfer Under USG Guidance
You may stay in our recovery room for a couple of hours (bring a book or your i-pad) and then head home. In the meantime we will give you final instructions.
If there are “extra” good quality embryos left over, you may be able to freeze them. This is called “embryo cryopreservation.” They can be used later or destroyed or donated.
On or after the day of your retrieval, and before the embryo transfer progesterone preparations / other medications are given to enhance implantation(the process by which the embryo adheres to the uterus) and to support early pregnancy (Luteal Support). Progesterone preparations can be in the form of injections/oral tablets/vaginal tablets/vaginal gel. Generally the dreaded painful injections (oil based progesterone injections) are not given unless absolutely required. The vaginal tablets/gel and oral tablets have given equivalent or better results. These medications are continued for 14 days after the embryo transfer.
Disadvantages of injectable progestrone –
- The principle disadvantage is that of a need for daily intramuscular injection.
- Also intramuscular progesterone administration may lead to redness, inflammation, tender wheals at the injection site and even sterile abscess formation can occur. This is the result of the long half life of the oil vehicle.
- Allergic reactions also have been noted with use of intramuscular progesterone injections.
Advantages of vaginal progestrone
- Vaginal route of administration provides targeted delivery. The active ingredients are transported directly from the vagina to the uterus, thus increasing the concentration of progesterone in the uterus and bypassing the systemic circulation. This increases the concentration in the target organ and reduces the risk of side effects via the “first uterine pass effect”.
- The gel produces an endometrial response that is equal to or advanced in comparison with that demonstrated by the IM route.
- The vaginal route is convenient and more acceptable to the patients since it does not hurt nor requires special equipments. It is rarely allergenic.
- It has been noted that low plasma & high uterine levels following vaginal administration makes it unnecessary to monitor serum progesterone levels, thus providing substantial cost savings.
Besides the progesterone, there really isn’t much going on for the next two weeks. In some ways, the two weeks after the transfer may be more difficult emotionally than the two weeks of treatment. During the previous steps, you will have visited your doctor perhaps every other day. Now, after transfer, there will be a sudden lull in activity. All you can do is wait the two weeks and see if pregnancy takes place. It can help to keep busy with your life during this wait time and avoid sitting and thinking about whether or not treatment will be successful.
After fourteen days, a blood test – serum beta hCG is done to know the outcome of the cycle. No fasting is required for the test. We will get the report by afternoon and we will call you with the report.
If the test is positive, the blood test will be repeated every 5th day. This will help us to monitor the progress of your pregnancy. You will need to keep taking the progesterone supplementation for another several weeks. A transvaginal ultrasound is done when the beta hCG values reach a particular level. This will help us to monitor the pregnancy. During every visit, your blood pressure and weight will be charted. Slowly the luteal phase support decreases and stops by 10-11 weeks. After this the pregnancy continues as a routine pregnancy.
We will also monitor whether or not the treatment led to a multiple pregnancy. If it’s a high-order pregnancy (3 or more), the option of reducing the number of fetuses may be discussed. This is a procedure called a “multifetal pregnancy reduction.” This is sometimes done to increase the chances of having a healthy and successful pregnancy.
Can an IVF cycle be cancelled? Why?
- If there are not enough follicles grow or if you’re at risk for severe ovarian hyperstimulation syndrome, your treatment cycle may be cancelled and the hCG shot will not be given.
- If treatment is cancelled because your ovaries didn’t respond well to the medications, we may recommend different medications to be tried on the next cycle. While not common, a cycle may also be cancelled if ovulation occurs before retrieval can take place.Once the eggs ovulate on their own, they can’t be retrieved.
- If the cycle is cancelled due to the risk of OHSS, we try and adjust the dose of gonadotrophins in the next cycle.
Cancellation happens in around 5 -6% of IVF treatment cycles. The chance of cancellation rises with age, with those older than age 35 and patients with severe PCOS are more likely to experience treatment cancellation.
What do you do when IVF Treatment Fails?
- If the pregnancy test is negative 12 to 14 days post-transfer, however, you will be asked to stop taking the progesterone, and you will wait for your periods to start. The next step will be decided the further course of treatment, after we review the entire history, the actual cycle, drugs given, response seen and the embryology details.
- Having a treatment cycle fail is never easy. It’s heartbreaking. It is however important, to keep in mind that having one failed cycle doesn’t mean that you won’t be successful ever. The first cycle can sometimes be a learning curve.
- The subsequent cycle always gives the best pregnancy rate.
- “Every failure is a stepping stone towards success” is true in IVF/ICSI cycles as in any other walk of life. So instead of crying on failure, one should understand the cause of failure in consultation with an IVF specialist (quality of eggs, implantation failure etc.), try to find solutions and appropriate treatment should be started with a fresh and optimistic state of mind.
What are the risks of IVF?
The assisted reproductive procedures have so far proven remarkably safe for both, the would be mother & her child. However, long term follow up studies are not yet available.
- The main concern is ovarian hyper stimulation (OHSS) in response to fertility drugs. This is usually very rare because of proper evaluation, judicious use of drugs and its accurate dosage and adequate monitoring.
- Anaesthesia risks are very low, same as any other minor surgical procedures.
- Sometimes, oocyte retrieval process can result in pelvic infection or bleeding or injury to adjacent organs like bladder or bowel, but this is generally avoided because the procedure is done under ultrasound guidance.
- As far as pregnancy is concerned, there is an increased chance of multiple pregnancies due to the transfer of two, three or sometimes more embryos. However , the risks for pregnancy i.e. complications per say during pregnancy due to IVF/ICSI&during delivery are unchanged.
Are there any birth defects or abnormalities in the child born through IVF / ICSI ?
Male infertility is known to be associated (in some cases) with chromosomal and other genetic anomalies. There is known to be an increase in gross chromosomal abnormalities such as balanced translocations in men with very low sperm counts. Also, about 5% of men with very low sperm counts have small areas of missing DNA on their Y chromosome (Y micro-deletion).Techniques such as ICSI will, in some cases, may lead to transmission of genetic problems that might cause infertility in male offspring, or could possibly be associated with other (at this time unknown) medical problems in the child.
As of now, there have now been many thousands of babies born after IVF with ICSI with follow-up after birth. Thus far, there has not been demonstrated to be any clear increased risk for birth defects as compared to IVF with conventional insemination.Most studies thus far have shown that the risk of birth defects after ICSI is the same as for babies conceived through IVF without ICSI, and for those conceived naturally. However, some studies have suggested that having IVF with or without ICSI might increase the risk for birth defects.
Some studies have shown that around 4% of babies born via assisted reproductive technology such as in vitro fertilization (IVF) may have major birth defects, such as heart and urogenital tract malformations. But these risks are not much different from what would be expected in the general population. The major birth defects seen in babies born via IVF and/or ICSI included heart defects and malformations of the urogenital tract, such as hypospadias (an abnormality in the position of the opening of the urethra in boys).
It is not fully understood whether these birth defects or genetic diseases are caused by the infertility treatment itself or the underlying reason for infertility.
SOME FREQUENTLY ASKED QUESTIONS RELATED TO IVF/ ICSI
How may visits to the fertility clinic are required?
- A total of around 8-10 visits are required to the clinic. Overnight hospitalization is NOT required.
Are injections painful?
- The injections, by & large are not painful.
- The injections are selected in such a way that they are highly purified and can be given subcutaneously (like insulin injections).
- They can be administered on the thigh or stomach with very thin & small needle (no.26).
- They can be self administered or administered by the partner.
- Self administration of injections gives you better control of the cycle, flexible schedule for taking injections and avoids daily visits to the doctor. Also it gives you a feeling of self empowerment and involvement in the whole process.
Will I gain weight with injections?
- The injections will not cause any weight gain.
I am a working woman. Do I need to take leave? How many days?
- A prolonged leave is generally not required.
- You will require a leave of one day on the day of ovum pickup.
- You may take a leave of around one week after embryo transfer to relax at home.
- BED REST IS NOT REQUIRED.
- All scientific studies have shown that bed rest does not in any improve the results in any way. In fact, bed rest is detrimental to your mental status. This may make the 2 weeks wait for the test a nightmare.
Is my husband required for all the visits?
- He is required just before starting IVF cycle for consultation & counseling.
- Then he is required on the day of ovum pickup to give a semen sample.
- But circumstances permitting, if he can accompany you for your visits, it is a great morale booster.
I have endometriosis. Does this affect my fertility & can it affect the success rate of IVF?
- Studies suggest that endometriosis probably does not interfere with IVF success rates.
- There are, however, some caveats. Repeated ovarian surgery, removal of an ovary, or removal of severe pelvic adhesions may compromise the ovaries’ ability to produce enough eggs to warrant retrieval. Also, eggs that arise from an ovary with a large endometrioma (ovarian endometrial cyst) may have a reduced fertility potential.
- Other researchers have suggested that antiphospholipid antibodies, more commonly seen in women who have endometriosis, may contribute to implantation failure unless treated.
- However, conflicting data suggest that although these antibodies may be seen more frequently in women with endometriosis, the benefits of treatment are as yet unproven.
Can fibroids interfere with IVF?
- Fibroids are benign tumors consisting of fibrous tissue & muscle which grow in the uterus.
- The significance of fibroids relates not only to their size but also their location.
- Even small fibroids located inside the cavity of the uterus (submucosal fibroids), where embryos need to implant may interfere with success and need to be removed.
- Fibroids that do not encroach on the cavity of the uterus are generally not significant unless they are larger than 4 cm in diameter and also if there are multiple fibroids causing significant uterine enlargement.
I have bilateral hydrosalpinx. I have been told to get operated before the IVF cycle. Does surgery change the outcome of the cycle?
- There are two possible reasons that a hydrosalpinx may decrease success.
- First, it may be a mechanical wash out of embryos from the fluid back flowing into the uterus around the time of implantation.
- Since the distal end of the tube is blocked, this fluid may leak into the uterus and disrupt implantation.
- It is well known that a very small amount of media must be used when embryos are transferred after IVF.
- Increased fluid decreases success. A second reason is that the fluid itself has been shown to be embryo toxic.
- Since most hydrosalpinges, arise from a previous infection, there may still be agents in this fluid that cause an inflammatory response that either alters the uterine environment, or the health of the conceptus (embryo)
Does acupuncture treatment help during IVF cycle?
- The theory is that acupuncture can affect the autonomic nervous system, which is involved in the control of muscles and glands, and could therefore make the lining of the uterus more receptive to receiving an embryo.
- Acupuncture seems to help some women because it improves circulation to the ovaries, which makes healthier eggs and to the uterus, by increasing the chances that the lining will be strong enough to hold the embryos.
- Acupuncture provides better circulation and better blood flow to the womb thus helps in continuation of pregnancy till term and avoid premature deliveries.
- Acupuncture can be a stress-reliever during an emotional time.
What can be done to improve sperm quality?
- Sperm quality on the day of egg retrieval is often related to what happened in the male’s body 3 months ago. This is because sperm development takes 3 months. Listed below are guidelines to help ensure the semen specimen is of the best possible quality.
- Keep the use of alcohol and cigarettes to a minimum before and during ART treatment. Do not use any “recreational” drugs.
- If any prescription medication has been taken during the last 3 months, notify the ART CLINIC.
- Do not sit in hot tubs, spas, Jacuzzis, or saunas frequently during or 3 months prior to the ART cycle.
- Do not begin any new form of endurance exercise during or 3 months prior to the ART cycle. Physical activity at a moderate level is acceptable and encouraged.
- Frequent ejaculation (every 2 to 3 days) is recommended.
- Refrain from ejaculation for 2-3 days, but not more than 5 prior to collecting the semen sample for the ART cycle.
Am I depleting my store of eggs by undergoing an ART cycle?
- A woman is born with a full complement of eggs.
- There are far more eggs than will ever be used during a normal lifetime and ART procedures have no measurable “lowering” effects.
Can I exercise while I’m undergoing IVF treatment?
- But, you should refrain from high-impact exercise and choose workouts such as walking, swimming, yoga or cycling.