ASK OUR DOCTORS - IVF MESSAGE BOARD

Ask our Doctors is a service on our website that allows you to privately and anonymously ask questions of our doctors. You don't have to be a patient; everyone is welcome to write in and ask anything you wish. We may post your question along with our doctor's answers in this section, but your identity will never be disclosed. Feel free to email questions to: askourdoctors@newhopefertility.com. We have organized your questions into the following categories which we are most commonly quizzed. You may be able to find your question already answered.

AM I A CANDIDATE FOR IVF | ABOUT OUR IVF TREATMENT | SIDE EFFECTS – HEALTH RISKS | EMBRYO & EGG FREEZING

Why is the number of eggs produced in a cycle often the focus of treatment? is this also true with natural intercourse and IUI?

The success of IVF, as in natural intercourse or IUI depends on the production of quality of eggs not the quantity. The production of more follicles will not necessarily make a difference, since many follicles will not be mature enough to have produced a viable egg in a given month. A very limited number of viable, good quality eggs are produced by patients greater than 37 years, no matter what the protocol or number of follicles.

I have heard a lot about Mini IVF, minimal stimulation IVF, and gentle IVF. What are the difference between all these protocols, and how do they differ from conventional IVF?

Conventional IVF protocols are designed to produce higher quantities of eggs by treating the patients with multiple daily injections and higher doses of medication. In addition the inconvenience and discomfort of injections, the side effects from increased medications are also greater, because growth of higher number of follicles means more ovarian swelling and greater potential risks.

Mini IVF, minimal stimulation IVF and gentle IVF follow more or less similar protocols. Use less oral medication with little or no injectable medications. This is meant to result in fewer eggs, but with the best quality the body can produce. It is safe, patient friendly and closer to the body’s natural rhythms. In addition to be cost-effective, this approach produces results which are comparable to conventional IVF protocols.

Does your center also perform conventional IVF, what are the criteria for selecting patients for conventional IVF?

Yes, conventional IVF is performed mainly for egg donors. They usually are less than 25 years of age, can potentially produce higher quality eggs in each stimulation cycle.

Who are the potential candidates for gentle stimulation IVF? What is your outcome with it?

Gentle stimulation IVF is suitable for all patients regardless of the age. It can be a successful way to approach patients that have been denied IVF treatment because of high day 3 FSH values, or patients over the age of 39 who have diminished ovarian reserves. The success rate is comparable to conventional IVF.

Can you explain what is the protocol for mini IVF for patients above 35 years?

The Mini IVF protocol or gentle stimulation protocol is very close to the natural way of producing mature egg. In this approach, the patient stays on Clomid (clomiphene citrate) starting from Day 2 or Day 3 of a menstrual cycle until her follicles have grown to a large size which is sufficient for ovulation. A small amount of injectable gonadotropins may be given for some patients to assist the follicles’ growth. The anti estrogenic Clomid can effectively inhibit the LH surge at the hypothalamus level regardless of the elevation of the estradiol concentration until the day before the oocyte maturation triggers. Clomid tricks the pituitary gland which produce additional FSH. One of the advantages of using Clomid is that the pituitary function continues normally, but in conventional IVF pituitary functions are usually suppressed with Lupron. Mini-IVF treatment therefore provides women the opportunity to utilize an inexpensive, well tested medication (Clomid) to produce a managable amount of good quality eggs for her IVF needs. The HCG injection is used to induce ovulation and is not needed in Clomid IVFs; a simple nasal spray of Lupron or its equivalent is sufficient to trigger the final oocyte maturation and ovulation. Mini IVF protocols also avoids the extended periods of progesterone injections used in the conventional IVF.

The patients over 35 may even respond better with the Mini IVF approach. Clomid challenge tests showed that the older women produced higher FSH than younger patients in response to clomid. It allows a woman’s body to select the best eggs to mature, there by reducing the role of embryologist and lab incubators in selecting good eggs from a large number of eggs produced by high stimulation.

I have heard that in the 80's clomiphene was the main method of stimulation for IVF and success rates were dismal... is it true? What about now?

Clomiphene citrate, discovered more than 60 years ago, is the most frequently prescribed medication in fertility treatments, even now. Comparing 80’s with the present is not an accurate measure because today’s pregnancy rates have improved over the past 25 years. Understanding the technical advancements in reproductive biology field has changed drastically with respect to patient management and obtaining a pregnancy compared to 1980s. The success of a medical treatment depends on providing the appropriate, cost effective and less risky treatment for patients in achieving better result. Mini-IVF meets all these criteria.

I have had multiple cycles of IUI and IVF. I remember I always received HCG to trigger ovulation. Why do you prefer Synarel as a trigger instead of HCG?

When the follicles finally reach the optimal size, the brain will produce a LH (luteinizing hormone) surge. This will trigger the oocyte(s) to undergo final maturation and prepare for the release of eggs, this process is called ovulation.

The natural LH is short lived and is very expensive to produce artificially. Alternatively conventional IVF and IUI uses HCG (human chorionic gonadotropin from the human placenta) or some times relay on Ovidrel (synthetic HCG) for triggering of ovulation prior to egg retrieval. Since the HCG has a much longer half life it stays longer in the body and it stimulates immature follicles which might then be recycled and become cysts in the following cycle.

Synarel (synthetic Lupron) is a GnRH agonist taken as a nasal spray. It stimulate the pituitary to produce a surge of LH. It is strong enough to induce ovulation on larger follicles. Its half life is very short so it seldomly stimulates small follicles. This allows the body to preserve the smaller follicles for future cycles, rather than stimulate them prematurely. This increases the likelihood of producing healthy eggs, and also allows women to continue cycles repeatedly without have to take breaks. This is especially advantageous for older patients who have limited ovarian reserve.

IVF MESSAGE BOARD QA - AM I A CANDIDATE FOR IVF

Can I still do IVF even though my cycles are irregular?

Yes, but the course of treatment will depend on the reasons for the irregularity. If you have diminished ovarian reserve, or slow follicular development, your protocol and monitoring schedule may be adjusted.

If I have no antral follicles visible on an ultrasound at the beginning of my cycle, will I still produce an egg?

Quite possibly, but it may take longer for the follicles to mature.

I've been trying to get pregnant for several years. I'm 38 and I have been seeing an RE for two years. My FSH is high, it has gone as high as 21. Is there anything I can do about this? And does having high FSH mean that my chances of getting pregnant are very small? I have not tried IVF yet because my RE will not allow me to start with high FSH.

Given your age, there is still a good chance you can get pregnant using your own eggs. Many REs using conventional FSH use injectable FSH (gonal-f or follistim), despite the fact that women with high FSH are already producing high levels on their own. At New Hope, we believe that women with high FSH should be given a chance to try IVF if it is warranted. While high FSH is usually an indication of diminished ovarian reserve, it does not necessarily indicate poor egg quality. We do not have any cut-offs for FSH. Our approach is to try with either minimal stimulation, or do a natural cycle. The goal is to produce a small number of follicles, but to try to get the best quality eggs your body can produce. High FSH itself is not an issue, as long as your body can produce at least one follicle. At New Hope, we emphasize quality of eggs, rather than quantity.

IVF MESSAGE BOARD QA - ABOUT OUR IVF TREATMENT

How many days will I be on stimulation medication before retrieval?

Most women are usually on medication for 9-13 days.

Why do you add some injectable FSH for some women during a cycle?

When a patient does not produce enough additional FSH with Clomid or Femora (most often these are patients with low baseline FSH), we sometimes add additional FSH to the protocol to help follicular development. This of course depends on the hormonal circumstances for each individual patient. That is why we individualize treatment for each patient.

Why don't you put people to sleep during egg retrievals? Doesn't it hurt?

Because a majority of our patients do minimal stimulation IVF, most patients create only a few follicles – but the best quality their body can produce. So when I do your egg retrieval, it is over quickly. I also use a small, more flexible needle than many doctors, which is less invasive and causes less discomfort. When a patient produces a large number of follicles in each ovary, the highly stimulated ovary is large and tender, making your retrieval painful. However, with minimal stimulation, ovary size remains very similar to that in a natural cycle. They are therefore easier to puncture during retrieval, and are less sensitive. Also, since most of our patients are awake doing the procedure, I am able to explain each step, so that they can understand and follow along. The patients also know immediately how many eggs are retrieved. We have a monitor set up with a view from the microscope, so that the patient can see the embryologists working as it is happening. Most patients tolerate these retrievals fine, and we recommend taking 500mg of Tylenol one hour before the procedure, and a small amount of valium a half hour before the procedure, to help you relax without putting you to sleep. If a patient has a particular problem, and needs to be sedated for some reason, we will provide it. There is an additional cost for IV sedation, because an anesthetist is required to be present. My staff and I will talk to you about the options, and help you make a decision you are comfortable with.

Why do you use a nasal spray to trigger ovulation, instead of an hCG injection?

Due to the fact that natural LH is short lived, and very expensive to produce synthetically, conventional IVF uses a hormone from the human placenta called human chorionic gonadotropin (hCG), or Ovidrel (synthetic hCG) as alternatives, in order to induce final egg maturation, or the "triggering" of ovulation prior to egg retrieval or IUI. The problem with hCG is that due to its long half life, it lasts much longer in the human body than natural LH and is more potent. Furthermore, in order to properly induce final oocyte maturation, a large amount of hCG (typically 10,000 IUs), is required, about equivalent to double the amount of total gonadotropins a patient typically receives in a conventional daily injection protocol. HCG not only induces ovulation, but also stimulates small follicles which might then be recycled, only to become cysts in the following cycle. It is common to find cysts in patients after cycles using hCG injections. In contrast, by using a GnRH agonist called Synarel (synthetic Lupron) in a diluted form taken as a nasal spray, it serves to stimulate the pituitary to produce a surge of LH, which therefore results in timed ovulation. It is h3 enough to induce ovulation in larger follicles, but too short-lived to stimulate small follicles. This allows the body to cultivate those smaller follicles for upcoming cycles, rather than stimulate them prematurely, causing them to become cysts. This increases the likelihood of the production of healthy eggs, and also allows women to cycle repeatedly without taking breaks. This is especially advantageous for older patients and those with limited ovarian reserve.

I have heard that using OCPs (aka BCPs) can cause over suppression and cause my ovaries not to respond. Why do you use OCPs for some women?

Some of our patients are given OCPs to regulate their cycles. Over suppression is not a concern, because once FSH starts to stimulate antral follicles, the follicles will grow. OCPs may just slow down the response time. Also, OCPs serve to suppress the ovaries prior to the start of a cycle, making it more likely for follicles to develop together, rather than create a dominant follicle which will be ready for ovulation before the other follicles have a chance to mature. In order for an egg to develop in the ovary and then be released, several hormonal events must take place. An area of the brain, called the hypothalamus, is responsible for regulating the hormonal signals that start the process. The estrogen in the pill shuts off these signals from the brain that tell the ovary to develop and release an egg. Without these signals, the egg does not develop and is not available to be released (ovulated) and pregnancy cannot occur. In addition, the pill has a few other effects on your body that decrease the likelihood of pregnancy. One of the hormones in the pill, progestin, makes the mucous thicker in the cervix and tubes so that it is more difficult for sperm to pass into the uterus and more difficult for the egg to move down the tube. Also, the progestin in the pill causes changes in the uterine lining that hinder implantation of the fertilized egg. When used in the fertility setting, the pill's ovarian suppression characteristics serve to "quiet" the ovaries. This is meant to allow a stimulated cycle to begin with all of the follicles at the same stage of development. Hopefully, this prevents a "lead follicle" from developing, increasing the chances of having more follicles mature at the same time. BCPs do not negatively affect fertility. There Is no evidence to indicate that BCPs have anything but a short term effect in the body. If someone has been on the pill for an extended period of time, there is no reason to wait after stopping the pill in order to begin fertility treatment. In fact, it is advantageous to begin a stimulated cycle immediately after stopping the pill. Many people express concern about "over suppression" with the pill. In some women, the pill has a more suppressive effect than in others, but the only result of this is that it may take some more time for the hormone levels to reach the point where stimulation becomes effective.

IVF MESSAGE BOARD QA - EMBRYO & EGG FREEZING

My husband and I (I'm 38) are trying to get pregnant at another clinic (tried 3 times over 8 months since there was wait time between cycles), so far we have been unsuccessful. But, they have been freezing excess embryos each cycle. I was excited (we have 5 embryos frozen) because I am 38 and want to be sure I have the chance to have 3 children (we are trying for our 1st now), but I read about Vitrification on your website and see that the thaw survival rate is low unless Vitrification is used. Then you also say that there are usually only 3-5 quality embryos each cycle; well they have been transferring that many each time. So, now I'm worried all my frozen embryos will either not be good or will not survive the thaw. Now it seems it was a waste to use their Conventional IVF method, the extra embryos will not get me another 2 children. How many frozen embryos do you think I need if I want 2 additional children, and what do you suggest I do? I'm worried I may be running out of time.

You have quite a dilemma. I would first want to examine why the first 3 attempts failed, but aside from that I suggest you have 36 blastocysts embryos for your 2 future children if you stick with conventional IVF without Vitrification as the freezing method; this assumes you'll plan 3 IVF attempts for each child for a total of 6 attempts. I arrive at this number using statistics and simple math. At 38 the live birth rate is 23.1% if 2.6 embryos are transferred with conventional IVF. And if your clinic is using the slow-dunk freezing method only half of your embryos will survive which means you'll need double the embryos. So, if you allow 3 attempts per future child and plan to transfer 3 embryos each time you'll need 18 total embryos frozen. Then, if only half of those thaw you'll need to double the amount to 36. Next, I recommend you bank these embryos during your next few cycles before getting pregnant now (meaning, don't have them do any transfers during those cycles until you have 36 embryos in your bank). Why? Because if you get pregnant at 38 the earliest you can start again is 39, assuming you will start right away. The older you get the lower your percentage of pregnancy is. So, presumably your eggs are better now than a year from now. The dilemma is whether or not you should continue to use conventional IVF. If you decide to use your next few cycles to bank embryos minimal stimulation IVF would be best for you because there is no wait time between cycles and your eggs get older and potentially less viable each month. Time is of the essence for all women over 35. Also, if you chose a clinic that used Vitrification you would need to freeze only half the embryos versus freezing them with the slow-dunk method. That means since the thaw rate is 98% with Vitrification you will need only 18 frozen embryos.

IVF MESSAGE BOARD QA - SIDE EFFECTS OF FERTILITY DRUGS � IVF RISKS

Do fertility drugs cause cysts?

Occasionally, depending on the previous month�s type and dosage of medication, and on follicular development. Sometimes a follicle that did not mature in one cycle may evolve into a cyst which appears the following cycle. Sometimes an HCG injection can facilitate cyst formation. Cysts do not necessarily mean that you cannot begin another cycle.

I have heard that Clomid can have a negative effect on the uterine lining. Under what circumstances do you prescribe it? Also, I have heard that Femora is a cancer drug. Why do you prescribe it in connection with infertility?

Both clomiphene citrate (Clomid), and letrozole (Femora) are oral medications used to stimulate ovulation. Letrozole is emerging as a viable alternative to clomiphene citrate for women undergoing ovulation induction and ovarian stimulation, although no broad scientific studies have et established the drug�s efficacy as the first course standard treatment. Several preliminary studies have shown letrozole to be useful, and it provides few side effects, especially for women whose uterine lining may be thinned out by clomiphene citrate. As to its exact mechanism, letrozole falls in the category of drugs known as nonsteroidal aromatase inhibitors, meaning it is highly specific in suppressing estrogen synthesis. Aromatase is an important enzyme prompting the creation of estrogen. If the body makes less estrogen, FSH level increases, follicular development increases, and ovulation is stimulated. Letrozole was originally developed for breast cancer treatment, as certain types of breast cancer cells slow their growth in response to decreasing estrogen levels. Some time ago, one journal published an article about a study in Canada in which a very limited number of patients showed an increase of neural tube defects in fetuses of women who had taken letrozole. However, there have been several subsequent larger studies which did not substantiate these findings. Since letrozole does not block the estrogen receptors, it is less effective than clomiphene citrate in preventing LH from surging. Therefore on rare occasions, premature ovulation can occur, so we monitor our patients taking letrozole more frequently. We have also observed that clomiphene citrate seems to work better for our younger patients, but we do not have conclusive data to support this yet. Generally, clomiphene citrate is used for women who are freezing embryos, and letrozole is used for older women who are doing fresh embryo transfers. At New Hope, we evaluate each patient�s individual needs and circumstances and choose medications accordingly. Letrozole has shown to be particularly helpful for a subset of women whose endometrial lining may become thin while taking clomiphene citrate. As an anti-estrogen, clomiphene citrate can limit the development of the endometrial lining, making it, we believe, more difficult for an embryo to implant. For reasons that aren�t quite yet clear, letrozole appears less likely to affect the uterine lining. Furthermore, letrozole has a short life span in the body whereas clomiphene citrate can last for 4-6 weeks following an oral dose. At New Hope, we are pleased with what we�ve seen so far with letrozole and we look forward to seeing the outcome of studies that are underway to further assess its efficacy as standard treatment.

I have heard that Clomid is bad for older women. Why do you use it for older women?

I do not believe that Clomid is bad for older women. Older women do even better with natural and low stimulation cycles (like with Clomid). Bear in mind that Gonal-F and Follistim are man-made FSH themselves. Repronex contains natural FSH, extracted from menopausal women because their FSH is very high. Clomid works by tricking the pituitary gland, causing a woman's body to produce additional FSH. In older women or “poor responders” we usually find high baseline FSH or “day 3” FSH due to lower ovarian reserve. These women generally produce higher FSH in response to Clomid, as demonstrated by responses to so-called Clomid challenge tests. It also provides gentler stimulation than injectables, and therefore does not recruit follicles that are not ready for the antral stage, resulting in improved quality of eggs retrieved, and allowing eggs which are not ready to have additional time in the ovaries. It allow women's bodies to select the best eggs, instead of getting a larger number eggs and letting the embryologists and lab incubator select the best eggs through in vitro embryo development.

I have heard that freezing embryos causes damage. Why do you do so many frozen embryo transfers?

Our lab is one of a handful in the U.S. to use a fast-freezing technique called vitrification. The use of vitrification on human embryos was pioneered by the Kato Clinic in Japan, with which we are proud to be affiliated. Using this technique, ice crystals do not have a chance to form, and therefore there is no damage to the embryos when they are thawed. Our frozen embryo survival rate is 98%.

How do you know I won't ovulate before my retrieval? If I don't take Lupron, how can this be controlled?

During the middle of a woman's menstrual cycle, when the lead follicle reaches 16-18 mm in diameter, the estrogen level reaches its peak. This estrogen peak triggers the estrogen sensor - the receptors in the brain, through so-called positive feedback. It tells the highest hormone-producing command center (the hypothalamus) to produce gonadotropin releasing hormone (GnRH), which tells the intermediate command center (the anterior pituitary) to produce leutenizing hormone (LH). The surge of LH triggers the final maturation of the egg. In conventional IVF, lupron (GnRH analogue) is used to down regulate (disable) the hypothalamus from producing GnRH, in order to prevent a sharp increase in LH. Clomid, an estrogen antagonist, blocks the estrogen sensor – the receptors in the brain - which in turn blocks the positive feedback loop, so the hypothalamus does not receive the signal to release a larger amount of GnRH. Clomid works as efficiently as lupron in preventing premature LH surge.