What Is In Vitro Fertilization?

In Vitro Fertilization is a high technology infertility treatment. Couples who have trouble conceiving, having failed to conceive for more than two years, often need to turn to a reproductive specialist who can evaluate and prepare them for this delicate procedure. With this procedure, most of the steps required to become pregnant are basically done outside the body in a specialized laboratory. The basic steps are as follows:

1. The ovary is stimulated to mature many egss. In a normal natural cycle, only one egg is matured an ovulated. With IVF, the goal is to have many, though not too many, eggs because the quality of eggs varies and we want to make sure we have at least one or two good quality eggs. The goal is not to have to repeat the IVF cycle again.

2. The ovary is evaluated by sequential ultrasound examinations to evaluate the response and measure the follicles. Follicles are what contain the eggs. They look like a black circle on ultrasound. The eggs are too small to be seen so we indirectly evaluate the egg by looking at the size of the follicle.

3. Once the follicles, that contain the eggs, are of appropriate size, indicating that the egg within is mature, the aspiration of the follicles is performed. This is a minor procedure whereby a needle is inserted through the vagina into the ovary under ultrasound guidance and the entire contest of the follicle, which includes the egg, is suctioned. Most clinics use some form of sedation for this because it can be painful. The eggs are aspirated into test tubes that the embryologist evaluates and isolates the eggs. These are then placed individually into petri dishes.

4. Sperm is either added to each egg (natural fertilization) or injected into each egg (ICSI) so that fertilization may occur. This will take 24 hours.

5. The eggs that fertilize are now placed into their individual petri dishes to allow for incubation. Incubation is done over a 3-5 day period. During this time, the fertilized egg will divide many times to evolve into a 6-8 cell embryo at 3 days or a blastocyst at 5 days. It's progress is monitored daily.

6. At 3 days from the retrieval or 5 days from the retrieval, the transfer is performed. The patient, with recommendations from the Physician, chooses which embryos to transfer and how many to transfer. These specific embryos are then isolated and placed into a very small and very flexible catheter in the embryology laboratory. The patient is placed into a transfer room, placed into the standard position for doing pap smears, and the cervix is prepared. The embryologist brings the embryo(s) into the transfer room and the Physician very gently slides the catheter into the uterus to a specific place. This location is verified by abdominal ultrasound examination. The embryo(s) is then deposited and the catheter gently and carefully removed. The embryologist will then take the catheter to the lab to verify that the embryo has not been re-aspirated.

7. The patient then takes medications to help support implantation of the embryo.

8. 8-12 days after the transfer, the pregnancy test is performed. If positive, we do pregnancy tests every-other day for four consecutive pregnancy tests. Since these tests measure the pregnancy hormone, BHCG, levels, we can see if the pregnany is progressing well by these four values.

9. If all goes well with the pregnancy tests, then the first ultrasound is scheduled in two weeks to confirm an intrauterine pregnancy and the number. This will be about 6 weeks gestational age based on the transfer date.

10. We then do a second ultrasound at 8 weeks gestation to verify a viable pregnancy.

At this point, the patient is then transferred to her Obstetrician to begin her prenatal care. For all infertility specialists this is a joyous occasion tempered by some sadness at not being able to follow the patient all the way through to delivery. When I began doing IVF, I was still practicing obstetrics and has the rare opportunity to deliver the babies that were conceived with our help. At this point in my practice career, I still do gynecology and I have much more time to focus on the infertility side of my practice as well. My patients benefit from still being able to receive gynecological advice as well as infertility advice.

INFERTILITY EVALUATION ABC'S

I thought I would share my approach to the infertility evaluation. I have seen many patients referred to me, who have not undergone a complete infertility evaluation. Many physicians approach this haphazardly, checking some things but not others. Like other disease states, in order to find the diagnosis, all the different possiblities must be ruled out. In 30% of cases, there is more than one problem, and in 30% of cases it involves both the man and women. Therefore all these systems must be checked. There are basically 9 steps that are required to become pregnant. These steps are a sequence of events, such that, if there is a disturbance in any part of the sequence, then the entire process fails. These steps are 1. Brain sends signals (FSH hormone) to the ovary to begin the ovulation process, and the Ovary begins the maturation of the egg > 2. Ovulation occurs where the egg is expelled from the ovary into the culdesac > 3. The egg has to find the fimbria of the tube. > 4. The egg enters the tube where the sperm needs to be waiting, such that, the sperm needs to have proceeded from the vagina into the cervix, into the uterus then into the tube. > 5. The sperm has to fertilize the egg. > 6. The egg begins developing and dividing and passes through the tube (7-days). > 7. The formed embryo now enters into the uterus. > 8. The embryo has to hatch. > 9. the embryo has to implant into the lining of the uterus. The infertility evaluation that is recommended, checks each one of these steps and I've listed them with the respective step in the sequence:


1. Hormone levels on cycle day # 2 or 3. This is to test to see if the hormone levels, that the brain is producing, are normal at the start of the cycle. This can also give an indication of how the ovary is functioning and able to be stimulated. If the FSH level is elevated, it could indicate that the ovary is already beginning to slow down and/or approaching menopause. If the FSH is elevated, some physicians will proceed with a Clomid challenge test to see if the ovary is past the point where it can be stimulated by fertility medications. The only way to see if the ovary is maturing an egg is to do an ultrasound, in sequence, and see if a growing ovarian follicle is present. This is not usually done as part of the basic infertility evaluation.

2. Mid-luteal progesterone test on cycle day # 20-22. The progesterone level is increased when ovulation occurs, so this in an indirect test of ovulation.

3. Laparoscopy. Any abnormalities in the culdesac, the part of the female pelvis where the egg passes through and where the fimbriated end of the fallopian tubes sit, such as endometriosis or adhesions or tubal abnormalities, can affect the eggs ability to be picked up by the tube. The only test for this is laparoscopy, where a scope is inserted through the belly button to look inside.

4. Hysterosalpingogram. Sperm and egg get together in the fallopian tube. A hysterosalpingogram (HSG) is done to test if the tube is open. This is an x-ray test where a dye is injected into the uterus and passes through the tubes. X-rays are taken in various intervals to confirm that the dye passes into the pelvis.

5. Semen Analysis. We do not have a test to see if fertilization can occur. Therefore, we test the sperm as an indirect method to assess its potential. This is done with a semen analysis. In this analysis we test for the number of sperm, the number of sperm that are swimming (motility)-which is also a measure of the number of live sperm, and the number of normally formed sperm (morphology). This is not just a test of numbers. It is an indirect indication of sperm function. If there is an abnormality then this may indicate that the sperm may not be able to fertilize an egg. The only way to assess if your husband's sperm can fertilize your egg is to remove your eggs and put them together with his sperm, then see what happens. That cannot be done without in vitro fertilization.

6. There is no test for this step, but the HSG indirectly gives evidence that the tube is open and the egg has the potential to pass through.

7. Hysteroscopy. The uterine cavity is tested by a procedure called a hysteroscopy. In this test, a scope is passed through the cervix and the uterine cavity is visualized directly to make sure it is normal. I do this test in my office but most gynecologists do this test in a surgery center.

8. There is no test for this step.

9. An endometrial biopsy is done at the end of the cycle, just before onset of menses, usually cycle day # 26-28. The biopsy tells us if the uterine lining is developed adequately for implantation.

10. Pelvic ultrasound. I do one additional test, which is a pelvic ultrasound. This allows me to assess the uterus, especially the muscle layer and anatomy, the ovaries to rule out cysts and tumors, and if there are any adnexal abnormalities (the areas around the ovaries). Sometimes a dilated tube can be seen.

THE INFERTILITY PATIENT AND THE INSURANCE COMPANY...THE ODD COUPLE.

Here is some advice regarding getting coverage for infertility testing. Consumers need to keep in mind that medical insurance companies are not your advocates. They make their money by keeping the premiums that you have paid, if you don't use them. Therefore, their goal is to keep as much of your money as they can (profit); and they have been doing a good job of it. Evaluation of their stock and company perfomance show that they are one of the best businesses to invest in because, despite a recession, they continue to make lots of money. That being said, here is one way that insurance companies shortchange infertility patients.

As many infertility patients know, once they determine that they have been unable to become pregnant, they need to undergo an evaluation. Also, patients undergoing higher level treatments, such as in vitro fertilization, are required to undergo testing as mandated by the FDA and CDC. In most cases, these tests are general health screening tests and not specifically infertility tests. They are tests such as infectious disease testing, hepatitis, AIDS, hormone testing, pelvic ultrasounds, etc. These are tests that are done for many reasons and for many diagnoses, not specifically or only for infertility. Coding requirements mandate that the most specific diagnosis is used when billing. Infertility, is not a very specific diagnosis. In most instances, there is a diagnosis that is a more specific illness, which as a consequence of their effect, can lead to or cause infertility. These are illnesses such as:

• irregular menstrual cycles


• polycystic ovarian syndrome


• sexually transmitted disease screening


• abnormal bleeding, endometriosis


• uterine fibroids, etc.

Make sure that your doctor or clinic is using the most specific diagnosis that they can.

In terms of insurance coverage, if you do not have infertility coverage, then insurance companies will not pay for infertility services. As mentioned above, many of the tests, if coded with the specific illness, are not infertility codes. Therefore, these tests should be covered. However, many, if not most, insurance companies will automatically flag your account if there is ANY reference to infertility. They then will deny all claims that can be related to infertility testing or treatment thereafter, including general health tests. Remember, their goal is to not pay for as much as possible and this is one way that they get away from paying for tests. Keep an eye on your EOB's, the statements you receive from your insurer that tells what they covered and did not cover. Also, check your test requisitions too and ask what diagnostic code they used. If they used an infertility code, ask if there is a more specific diagnosis code pertaining to your condition that they can use. Then if the lab test is denied, YOU need to contact your insurance company and file an appeal. It should be done in writing and keep all records of your attempts. Do not rely on the doctor's office to do this for you. Remember, you are the insurance company's client, NOT the doctor. You have more leverage than they do. Ultimately, if the insurance company denies a justified claim, that you have repeatedly appealed, you can go to the next level of appeal, which is the Commissioner of Insurance for your State and file a complaint.

Word of Caution! I am NOT advocating that you commit fraud. If there is no other diagnosis or illness that applies to your test, and infertility is the only diagnosis that can be used, then that is the correct diagnosis. In that case, the insurance company has the right to deny the claim. Do Not ask your doctor to lie about your condition by using another diagnosis code. Both you and your doctor can be criminally liable if you commit fraud. Remember, honesty is your greatest weapon when dealing with the insurance companies. They are required to be honest with you as well. If you are not honest, you have nothing to stand on to refute their denial. If you are, and your claim is legitimate, then the insurance company has to accept your claim. You are paying them for the services they have promised to provide. Be a wise and diligent consumer and make sure they are providing you with all the services you are entitled to.

HORMONE REPLACEMENT THERAPY

Five years ago, the NIH stunned the country by publishing a study regarding hormone replacement therapy (HRT). This study refuted ALL the previous studies heralding the benefits of HRT, by claiming that it increased the incidents of heart disease and breast cancer. This sensationalized conclusion led millions of women to abandon their HRT, leading to mass suffering among women. I remember seeing these headlines in very well placed articles in various newspapers. It aggravated me because I reviewed their data and found one serious flaw that should have negated all their results: their data was NOT STATISTICALLY SIGNIFICANT.

Whenever scientific studies are performed, their results are measured by various mathematical tests to see if in fact the findings are really showing what they purport to show. We call this statistical significance. Results are either statistically significant or not. There is no middle ground. The WHI authors tried to create a new term, "almost statistically significant." There is no almost. It is either yes or no. If it is not yes, then the results are not justified. Since the release of this study, multiple newer analyses of the same data have refuted the author's original claims. In addition, the average age of women in the study was 60 and a full 10 years after starting menopause. The conclusion that readers should draw, after all the recent backpedaling, is that the findings of this study from 5 years ago were incorrect and should be ignored. They also don't apply to recently menopausal or perimenopausal women.

So what do you do now?

• If a woman is postmenopausal and does not take HRT for 10 years or more after menopause, then there will be no benefit to starting. In fact, estrogen could be detrimental at that point. However, several recent studies and re-analysis of WHI data have shown, in confirmation of previous pre-WHI studies, that HRT is beneficial to women if begun at or near menopause.
• Benefits include a reduction in heart disease, cognitive function, skin health, vaginal health and bone health.
• Most significant, is a reduction in heart disease, which is the number one cause of death in women after menopause.
• In addition, the review of the data, contrary to the original WHI conclusions, is that there is a reduction in the incidence of breast and colon cancer. The studies are too numerous for me to cite here, but suffice it to say that the data is overwhelming.

I have continued to recommend HRT in my peri-menopausal and menopausal patients, despite the initial WHI broadcasts. I'm glad I did because now we know that it is protective of their health. For me it only makes sense. The most healthy, happy and vigorous parts of a women's life is the pre-menopausal days when estrogen was abundant. When women become menopausal, their health, body and mind begin to deteriorate, as a result of the lack of estrogen. In fact, estrogen is the youth hormone and should be continued. When my patients present in their 40's with peri-menopausal symptoms of irregular or abnormal periods, insomnia, difficulty concentrating or remembering, mood swings, lack of energy or general lack of well-being, that is the time that I recommend HRT. Usually, I use a low-dose birth control pill because it has sufficient estrogen and is easy to take. In women who don't have a uterus (due to hysterectomy) I give a higher dose estrogen without progesterone. At this point, it is unknown how long a woman should take estrogen. In my opinion, since the average lifetime of women is increasing, currently it is 86 years old, women should continue with the estrogen indefinitely. At some point, maybe it won't be necessary but for now, I think there is very little risk and lots of youth to gain.

CHOOSING A FERTILITY SPECIALIST

I've often been asked by patients, when and how to choose a fertility specialist. The question they have is whether to stay with their current OB/GYN physician or seek out an infertility specialist. First, if you are undergoing some evaluation and possibly treatment by a Family Practice physician or General practitioner, you're in the wrong hands. Your doctor may feel he or she can do infertility, and may have had some exposure to infertility in their training, but it was hardly enough for them to be evaluating and/or treating infertility patients. I have even had patients that were under the care of physician assistants and nurse practitioners! These are the wrong providers for your problem. Speciality care should be done by a specialist, an OB/GYN physician, Infertility specialist or Reproductive Endocrinologist, not a general practitioner. See "Infertility Evaluation" for more information.

The easy answer to the question is seek out the physician that you feel you need to see. If you want a basic level of evaluation and treatment, or want minimal intervention, then most OB/GYN physicians have adequate training and knowledge of infertility to help you. However, this varies among OB/GYN docs so make sure your doc has this knowledge. One good way of screening is to simply ask what levels of treatment they provide: Clomid ovulation induction, Gonadotropin ovulation induction or Insemination (artificial insemination)? I would choose a doc that can do at least insemination. If they don't do that, then their training and knowledge is probably not adequate for your needs. The problem with docs that only do a little, is they tend to get stuck in the little that they can do and are slow to refer you to a higher level of care. For example, a doc that can only do Clomid ovulation induction, but not insemination, tends to treat their patients for months with just Clomid, often without even doing a complete infertility evaluation to see if this is the best treatment. Clomid ovulation induction should probably not be done for more than 6 months. If your doc gives you a prescription for Clomid, that is a year's supply, and says call me if you miss your period, then you need to find another doctor. Or, if you go to your doctor with your infertility problem and the doctor sends you away with a Clomid prescription before even suggesting an infertility evaluation, then that is another sign that you need to seek out a different doctor. As a consequence, you end up losing valuable time, and money. A good OB/GYN and Infertility specialist will lay out a clear and concise plan for evaluation and treatment, and give a defined timeline for each.

However, that being said, you may also want to avoid the clinic that provides only IVF, because they will not offer other choices of evaluation or treatment. If you are just starting your infertility care and evaluation, that may be the wrong choice for you. Many large IVF clinics are like that. They only provide IVF. You want an infertility specialist that offers IVF, in addition to, a broader level of evaluation and care. Find someone who can provide all levels of infertility evaluation and treatment.

So, when should you seek a specialist? The answer is when you feel you need a specialist. For some that will be right from the start, when you realize you are not getting pregnant. For others, that will not be until they have exhausted their options with their Ob/Gyn doctors. My advice is this: if you are under 35 years old, then either a well-trained Ob/Gyn doc or an infertility specialist will do, depending on your problem. If you decide to go to an Ob/Gyn doc, then do not spend more than 6 months on a treatment plan. If it doesn't work by that time, then it's time to move on. If you are over 35, then you should go directly to see an infertility specialist, because time is working against you. Also, if you have tubal blockage, stage 3 or 4 endometriosis, a very bad semen analysis or failed four IUI's, then you should see an infertility sub-specialist directly.

The Disclaimer

I am pleased to be writing a blog on women's health issues. I hope that by doing so I can help people by giving them the information they need from an expert in the field. Please keep in mind, though, that the information provided in this blog is not meant to be a medical opinion about your specific case. The problems of every patient are unique and should be addressed by their physician in a face-to-face conversation and thorough work-up. You are welcome to bring up questions about my postings with your doctor. However, no one should assume that this blog is a source of medical care. I believe that reading it might offer some insights into medicine that might not otherwise be available in the general media.

Welcome From Dr. Ramirez

Welcome to the first installment of the Women's Health and Fertility Blog. My name is Dr. Edward Ramirez and I am a gynecologist and infertility specialist practicing in Monterey, California (http://www.montereybayivf.com/). My goal for this blog is to educate women about their health and to help couples who face infertility. Over the past 13 years I have experienced the ups and downs that come along with a busy gynecology and infertility practice. Obviously, the ups have been great but the downs have made me realize that there is much still to be achieved in medicine to help women overcome their health problems. I hope to help people gain a better understanding of what is in the forefront in women's health and perhaps help them to seek better care for the problems they are currently facing. Thank you and please stay tuned!