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Archive for the ‘FSH’ tag

Is Your Biological Clock Running Out?

By David Kreiner, MD

January 10th, 2014 at 10:35 pm

 

image courtesy of photo stock/freedigital photos.net

Tears start to course down the cheeks of my patient, her immediate response to the message I just conveyed to her. Minutes before, with great angst anticipating the depressing effect my words will have on her, I proceeded to explain how her FSH was slightly elevated and her antral follicle count was a disappointing 3-6 follicles. I was careful to say that though this is a screen that correlates with a woman’s fertility, sometimes a woman may be more fertile than suspected based on the hormone tests and ovarian ultrasound. I also said that even when the tests accurately show diminishing ovarian reserve (follicle number), we are often successful in achieving a pregnancy and obtaining a baby through in vitro fertilization especially when age is not a significant factor.

These encounters I have with patients are more frequent than they should be. Unfortunately, many women delay seeking help in their efforts to conceive until their age has become significant both because they have fewer healthy genetically normal eggs and because their ability to respond to fertility drugs with numerous mature eggs is depressed. Women often do not realize that fertility drops as they age starting in their 20s but at an increasing rate in their 30s and to a point that may often be barely treatable in their 40s.

A common reason women delay seeking help is the trend in society to have children at an older age. In the 1960’s it was much less common that women would go to college and seek a career as is typical of women today. The delayed childbearing increases the exposure of women to more sexual partners and a consequent increased risk of developing pelvic inflammatory disease with resulting fallopian tube adhesions.

When patients have endometriosis, delaying pregnancy allows the endometriosis to develop further and cause damage to a woman’s ovaries and fallopian tubes. They are more likely to develop diminished ovarian reserve at a younger age due to the destruction of normal ovarian tissue by the endometriosis.

Even more important is that aging results in natural depletion of the number of follicles and eggs with an increase in the percentage of these residual eggs that are unhealthy and/or genetically abnormal.

Diminished ovarian reserve is associated with decreased inhibin levels which decreases the negative feedback on the pituitary gland. FSH produced by the pituitary is elevated in response to the diminished ovarian reserve and inhibin levels unless a woman has a cyst producing high estradiol levels which also lowers FSH. This is why we assess estradiol levels at the same time as FSH. Anti-Mullerian Hormone (AMH) can be tested throughout a woman’s menstrual cycle and levels correlate with ovarian reserve. Early follicular ultrasound can be performed to evaluate a woman’s antral follicle count. The antral follicle count also correlates with ovarian reserve.

By screening women annually with hormone tests and ultrasounds a physician may assess whether a woman is at high risk of developing diminished ovarian reserve in the subsequent year. Alerting a woman to her individual fertility status would allow women to adjust their family planning to fit their individual needs.

Aggressive fertility therapy may be the best option when it appears that one is running out of time. Ovulation induction with intrauterine insemination, MicroIVF and IVF are all considerations that speed up the process and allow a patient to take advantage of her residual fertility.

With fertility screening of day 3 estradiol and FSH, AMH and early follicular ultrasound antral follicle counts, the biological clock may still be ticking but at least one may keep an eye on it and know what time it is and act accordingly.

* * * * * * * * * * * * * * * * *

Did you realize that aging is not the only factor in the biological clock race? Did you know that certain conditions, like endometriosis, can play a part, too?

 

Photo credit: http://www.freedigitalphotos.net/images/agree-terms.php?id=10049499

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IVF 101: Infertility Terms Defined

By David Kreiner MD, and Tracey Minella

March 8th, 2012 at 11:07 pm

Don’t be a deer in the headlights when it comes to infertility diagnoses and treatments. Yes, there’s a lot to learn. Yes, it can be overwhelming, leaving you a bit glassy-eyed. But the good news is that you can go to the head of the class by the time you finish reading this post.

Dr. David Kreiner of Long Island IVF gives you the low-down and the lingo. It’s everything you need to know, from A to… well… P. And what better letter to stop at? “P” is for pregnant:

“Why me? My wife never had any infections, surgery or any other problem? I have no difficulty ejaculating and there’s plenty to work with so why can my friends and neighbors and coworkers get pregnant and we can’t?”

I hear these questions daily and understand the frustrations, anger and stress felt by my patients expressing these feelings through such questions. There are many reasons why couples do not conceive. An infertility workup will identify some of these. A semen analysis will pick up a male factor in 50-60% of cases. A hysterosalpingogram will locate tubal disease in about 20% of cases. Another 20-25% of women do not ovulate or ovulate dysfunctionally. A post coital test may identify that the problem is that the sperm is not reaching the egg. It may not be able to swim up the cervical canal into the womb and up the tubes where it should normally find an egg to fertilize. When these tests are normal a laparoscopy may be performed to identify the 20-25% of infertile women with endometriosis. However, even when this is normal and there is no test that logically explains the lack of success in achieving a pregnancy; an IVF procedure may both identify the cause and treat it successfully.

What is IVF?

In Vitro Fertilization, IVF, is the process of fertilizing a woman’s eggs outside the body in a Petri dish. Typically, a woman’s ovaries are stimulated to superovulate multiple eggs with gonadotropin hormones, the same hormones that normally make a woman ovulate every month. Injections of these hormones are usually performed by either the husband or wife subcutaneously in the skin of the lower belly with a very tiny needle. It takes 9-14 days for the eggs to mature. She will then take an HCG injection which triggers the final stage of maturation 35-36 hours prior to the egg retrieval. This is performed in an operating room, usually with some anesthetic. The eggs are inseminated in the lab and 3-5 days later, embryos are transferred into the uterus with a catheter placed transvaginally through the cervix into the womb.

What is ICSI?

Some times even in the presence of a normal semen analysis, and normal results on all the infertility tests, fertilization may not occur without microsurgically injecting the sperm directly into the egg. This procedure is called Intracytoplasmic Sperm Injection or ICSI and may achieve fertilization in almost all circumstances where there is otherwise a sperm cause for lack of fertilization.

If it looks like a sperm and swims like a sperm, why doesn’t it work like a sperm?

A South African gynecologist, Thinus Kruger, discovered that small differences in the appearance of sperm affected the sperm’s ability to fertilize an egg. In 1987, Thinus demonstrated that when we used the very strict Kruger criteria for identifying a normal sperm, we were able to identify most men who had normal semen analyses and were yet unable to fertilize their wife’s eggs. Most of these couples suffered from unexplained infertility except now utilizing the Kruger criteria for sperm morphology we were able to identify the problem. Today, these couples are successfully treated with the ICSI procedure.

Old eggs?

As women age, the percentage of genetically abnormal eggs increases. These older eggs are less likely to fertilize, divide normally into healthy embryos or result in a pregnancy. When older women do conceive they are more likely to miscarry then when they were younger. Aging of eggs begins in the 20’s but accelerates after age 35. This is why a woman’s fertility drops as she gets older. The age at which it becomes significant for a woman varies. Some women in their 30’s have significant aging of their egg. Others less so and may have a good number of healthy eggs into their 40’s.

ABC’s of IVF

Assisted Hatching is when the embryologist makes a hole in the shell around the embryo called the zona pellucidum. This is performed minutes prior to embryo transfer and may be performed chemically with acid tyrodes, mechanically with a micropipette or with a laser. It is commonly believed that older eggs may lead to embryos with a thicker or harder shell that may prevent the natural hatching of an embryo that must occur prior to the embryo implanting into a woman’s lining of her womb.

Blastocyt embryo transfers occur on day 5 or 6 after the egg retrieval. This is the embryonic stage when an embryo normally implants into the womb. These embryos have been selected to be healthier by virtue of the fact that they have made it to this stage. Some believe that a woman’s uterus may be more receptive to an embryo implanted at this stage. Statistically, the pregnancy rates for women who have had blastocysts transferred is higher than when the same number is transferred on day 3 using “cleaved” embryos of 4-10 cells. As the advantage of the blastocyst transfer may be only a matter of selection, it is thought that there may be no advantage if the embryologist is able to select just as well the best embryos to transfer on day 3.

Bravelle – Brand of FSH, follicle stimulating hormone which is a gonadotropin used to stimulate a woman’s ovaries to superovulate and make multiple eggs mature during the IVF cycle.

Cetrotide – Brand of Gonadotropin Releasing Hormone Antagonist that prevents a woman’s pituitary gland from producing LH, luteinizing hormone. LH increases can trigger premature ovulation and stimulate testosterone and progesterone production which can be harmful to a woman’s egg production and prematurely mature the lining of womb potentially affecting implantation.

Co-culture of a woman’s endometrial cells from the uterine lining or granulosa cells from aspirated ovarian follicles along with the embryos in the same culture dish is thought to provide growth factors for the embryos which may improve the health and growth of the embryos.

Cleavage Stage Embryos are 2-10 cell embryos transferred on day 2 or 3. They are often graded by their lack of fragmentation and granularity of the inside of the cell cytoplasm; A to D or 1to 5 with A or 1 being the best grade.

Embryo Glue is a protein supplement to the transfer media prepared minutes prior to transfer to make the embryo more likely to stick to the lining of the womb. It is believed that some embryos may not implant since they are not adhering to the lining and do not get an opportunity to burrow into the endometrium.

Estradiol is produced by the granulosa cells of the follicle which surround the egg in the ovary. As follicles are stimulated and grow they produce more estradiol. We measure estradiol to monitor development of the follicles. It also helps to prepare the lining of the womb for implantation.

Follistim – Brand of FSH, follicle stimulating hormone which is a gonadotropin used to stimulate a woman’s ovaries to superovulate and make multiple eggs mature during the IVF cycle.

Ganirelix – Brand of Gonadotropin Releasing Hormone Antagonist that prevents a woman’s pituitary gland from producing LH, luteinizing hormone. LH increases can trigger premature ovulation and stimulate testosterone and progesterone production which can be harmful to a woman’s egg production and prematurely mature the lining of womb potentially affecting implantation

Gonal F – Brand of FSH, follicle stimulating hormone which is a gonadotropin used to stimulate a woman’s ovaries to superovulate and make multiple eggs mature during the IVF cycle.

Gonadotropins – FSH, follicle stimulating hormone and LH, luteinizing hormone stimulate the follicles in the ovary to mature and produce ovarian hormones, estradiol, testosterone and progesterone. It also is used to stimulate a woman’s ovaries to superovulate and make multiple eggs mature during the IVF cycle. We adjust the ratio of FSH and LH to achieve goals of optimal follicular development and maturation while trying to minimize the risk of hyperstimulation. Typically we administer the gonadotropins to the woman for 8-14 days before giving her HCG 35-36 hours prior to the egg retrieval

HCG is human chorionic gonadotropin, the pregnancy hormone we measure to see if your wife is pregnant. We follow the numbers to monitor the growth and health of the pregnancy. HCG has the same biological effect as LH and therefore can be used to mature the egg in the same way as if it were getting ready to ovulate. We therefore administer HCG to women 35-36 hours prior to the egg retrieval. Brand names for HCG include Pregnyl and Ovidrel.

HMG – Human Menopausal Gonadotropins are purified from the urine of menopausal women since they have high levels of FSH and LH. Menopur and Repronex are brands of HMG used in IVF stimulations containing a 1:1 ratio of FSH to LH. We adjust the ratio of FSH and LH to achieve goals of optimal follicular development and maturation while trying to minimize the risk of hyperstimulation. Adding pure FSH, i.e. Bravelle, Follistim or Gonal F will increase the ratio of FSH to LH which may be desirable especially early in a stimulation. Some patients may not need any supplemental LH and are stimulated with FSH only. LH is sometimes added towards the end of a stimulation to minimize the risk of hyperstimulation syndrome.

Hyperstimulation syndrome is a condition which occurs approximately 3% of the time as a result of superovulation of a woman’s ovaries with gonadotropins. A woman’s ovaries become enlarged and cystic, fluid accumulates in her belly, and occasionally around her lungs. When it becomes excessive, it may make it uncomfortable to breathe. We remove this excess fluid with a needle. Women can also become dehydrated and put them at risk of developing blood clots. We therefore recommend fluids high is salt content like V 8 and Campbell’s chicken soup. We give patients baby aspirin to prevent clot formation. It may also be recommended to freeze all the embryos and postpone the transfer to a later cycle as pregnancy can significantly exacerbate Hyperstimulation syndrome.

ICSI – Some times even in the presence of a normal semen analysis, and normal results on all the infertility tests, fertilization may not occur without microsurgically injecting the sperm directly into the egg. This procedure is called Intracytoplasmic Sperm Injection or ICSI and may achieve fertilization in almost all circumstances where there is otherwise a sperm cause for lack of fertilization

Lupron is a Gonadotropin Releasing Hormone Agonist that must be administered after a woman ovulates or concurrent with progesterone or oral contraceptive pills to effectively suppress gonadotropins. Lupron prevents a woman’s pituitary gland from producing LH, luteinizing hormone. LH increases can trigger premature ovulation and stimulate testosterone and progesterone production which can be harmful to a woman’s egg production and prematurely mature the lining of womb potentially affecting implantation

Monitoring of a woman’s stimulation with gonadotropins is performed by transvaginal ultrasound examination of her ovarian follicles and blood hormone levels. The gonadotropin doses can be adjusted according to the results of the monitoring. The timing of the HCG and subsequent egg retrieval are likewise based on the monitoring. Typically, a woman need not be monitored more frequent than every 3 days initially but may need daily monitoring as she approaches follicular maturation to determine timing of the HCG injection and retrieval.

Morula is the stage between the cleavage stage embryo and blastocyst. It is when the embryo is a ball of cells.

Oral contraceptive pills are often given prior to the stimulation to help time stimulation starts and bring a woman’s reproductive system to a baseline state from which the stimulation may be initiated.

Progesterone is an ovarian hormone that prepares the lining of the womb for implantation. We measure it during stimulation to check if the lining is getting prematurely stimulated. We add it to the woman after the retrieval to better prepare the lining and continue it as needed to help sustain the implanted embryo until the placenta takes over production of its own progesterone.

* * * * * *

Did you find this helpful? What was the most important piece of info you got from this post?

 

Photo credit: http://www.publicdomainpictures.net/view-image.php?image=14704&picture=deer

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Is Your Biological Clock Running Out?

By Tracey Minella and David Kreiner MD

January 6th, 2012 at 12:00 am


So, we just counted down the minutes on the regular clock, ringing in a brand new year. Did that remind you of anything? Maybe some other clock that is ticking down and causing you to fidget a bit?

You know which clock I mean: THE BLASTED BIOLOGICAL CLOCK!

I’ve always hated this term. Probably because I used to hit its SNOOZE button for years. It used to nag at me in the back of my mind as I pursued my education and got settled in my career…especially since I married young. And when it wasn’t in the back of my mind, it was being shoved smack in my face by the rude comments of nosy jerks, collectively known as “the masses of asses”. We’ve all got ‘em.

If you’re wondering whether your biological clock is really running out, this post by Dr. David Kreiner may be enlightening:

Tears start to course down the cheeks of my patient, her immediate response to the message I just conveyed to her. Minutes before, with great angst anticipating the depressing effect my words will have on her, I proceeded to explain how her FSH was slightly elevated and her antral follicle count was a disappointing 3-6 follicles. I was careful to say that though this is a screen that correlates with a woman’s fertility, sometimes a woman may be more fertile than suspected based on the hormone tests and ovarian ultrasound. I also said that even when the tests accurately show diminishing ovarian reserve (follicle number), we are often successful in achieving a pregnancy and obtaining a baby through in vitro fertilization especially when age is not a significant factor.

These encounters I have with patients are more frequent than they should be. Unfortunately, many women delay seeking help in their efforts to conceive until their age has become significant both because they have fewer healthy genetically normal eggs and because their ability to respond to fertility drugs with numerous mature eggs is depressed. Women often do not realize that fertility drops as they age starting in their 20s but at an increasing rate in their 30s and to a point that may often be barely treatable in their 40s.

A common reason women delay seeking help is the trend in society to have children at an older age. In the 1960’s it was much less common that women would go to college and seek a career as is typical of women today. The delayed childbearing increases the exposure of women to more sexual partners and a consequent increased risk of developing pelvic inflammatory disease with resulting fallopian tube adhesions.

When patients have endometriosis, delaying pregnancy allows the endometriosis to develop further and cause damage to a woman’s ovaries and fallopian tubes. They are more likely to develop diminished ovarian reserve at a younger age due to the destruction of normal ovarian tissue by the endometriosis.

Even more important is that aging results in natural depletion of the number of follicles and eggs with an increase in the percentage of these residual eggs that are unhealthy and/or genetically abnormal.

Diminished ovarian reserve is associated with decreased inhibin levels which decreases the negative feedback on the pituitary gland. FSH produced by the pituitary is elevated in response to the diminished ovarian reserve and inhibin levels unless a woman has a cyst producing high estradiol levels which also lowers FSH. This is why we assess estradiol levels at the same time as FSH. Anti-Mullerian Hormone (AMH) can be tested throughout a woman’s menstrual cycle and levels correlate with ovarian reserve. Early follicular ultrasound can be performed to evaluate a woman’s antral follicle count. The antral follicle count also correlates with ovarian reserve.

By screening women annually with hormone tests and ultrasounds a physician may assess whether a woman is at high risk of developing diminished ovarian reserve in the subsequent year. Alerting a woman to her individual fertility status would allow women to adjust their family planning to fit their individual needs.

Aggressive fertility therapy may be the best option when it appears that one is running out of time. Ovulation induction with intrauterine insemination, MicroIVF and IVF are all considerations that speed up the process and allow a patient to take advantage of her residual fertility.

With fertility screening of day 3 estradiol and FSH, AMH and early follicular ultrasound antral follicle counts, the biological clock may still be ticking but at least one may keep an eye on it and know what time it is and act accordingly.

* * * * * * * * * * * * * * * * *

Did you realize that aging is not the only factor in the biological clock race? Did you know that certain conditions, like endometriosis, can play a part, too?

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To Do List: Annual Fertility Screening

By Tracey Minella and David Kreiner MD

December 8th, 2011 at 8:06 pm


As the year winds down and you reflect on the past, and make resolution for the future, it pays to consider an annual fertility screening. Some of you may be well into treatment already, but others may just be starting out with their family-building plans…or may be putting off starting a family or adding to their family. It may be wise to have a baseline or annual fertility screening done, just to help rule out identifiable and underlying fertility problems you may already have and are unaware of. Armed with the knowledge a screening gives you, you can make a more informed decision about how long you may want to wait before beginning or resuming your family building plan.

Dr. Kreiner explains what a fertility screening means:

Fertility screening starts with a blood test to check the levels of FSH (follicle stimulating hormone), estradiol and AMH (antimullerian hormone). The FSH and estradiol must be measured on the second or third day of your period. The granulosa cells of the ovarian follicles produce estradiol and AMH. The fewer the follicles there are in the ovaries the lower the AMH level. It will also mean that less estradiol is produced as well as a protein called inhibin. Both inhibin and estradiol decrease FSH production. The lower the inhibin and estradiol the higher the FSH as is seen in diminished ovarian reserve. The higher the estradiol or inhibin levels are then the lower the FSH. Estradiol may be elevated especially in the presence of an ovarian cyst even with failing ovaries that are only able to produce minimal inhibin. However, the high estradiol reduces the FSH to deceptively normal appearing levels. If not for the cyst generating excess estradiol, the FSH would be high in failing ovaries due to low inhibin production. This is why it is important to get an estradiol level at the same time as the FSH and early in the cycle when it is likely that the estradiol level is low in order to get an accurate reading of FSH.

The next step is a vaginal ultrasound to count the number of antral follicles in both ovaries. Antral follicles are a good indicator of the reserve of eggs remaining in the ovary. In general, fertility specialists like to see at least a total of eight antral follicles for the two ovaries. Between nine and twelve might be considered a borderline antral follicle count.

As you start to screen annually for your fertility, what you and your doctor are looking for is a dramatic shift in values from one year to the next.

What Does the Screen Indicate?

A positive screen showing evidence of potentially diminishing fertility is an alarm that should produce a call to action. When a woman is aware that she may be running out of time to reproduce she can take the family-planning reins and make informed decisions. The goal of fertility screening is to help you and every woman of childbearing years make the choices that can help protect and optimize your fertility.

Although none of these tests is in and of themselves an absolute predictor of your ability to get pregnant, when one or more come back in the abnormal range, it is highly suggestive of ovarian compromise. It deserves further scrutiny. That’s when it makes sense to have a discussion with your gynecologist or fertility specialist. Bear in mind, the “normal” range is quite broad. But when an “abnormal” flare goes off, you want to check it out.

It’s important to remember that fertility is more than your ovaries. If you have risk factors for blocked fallopian tubes such as a history of previous pelvic infection, or if your partner has potentially abnormal sperm, then other tests are in order.

Regardless of the nature or severity of the problems, today, with Assisted Reproductive Technology there is a highly effective treatment available for you.

* * * * * * * * * * * **

Did you put off a fertility screening… and end up regretting it? If so, what advice do you have for other women who may be doing the same thing?

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Is Your Biological Clock Running Out?

By Tracey Minella and David Kreiner MD

May 19th, 2011 at 9:02 am

I’ve always hated this term.

It used to nag at me in the back of my mind as I pursued my education and got settled in my career…especially since I married young. And when it wasn’t in the back of my mind, it was being shoved smack in my face by the rude comments of nosy jerks, collectively known as the "masses of asses".

If you’re wondering whether your biological clock is really running out, this post by Dr. David Kreiner of East Coast Fertility may be enlightening:

Tears start to course down the cheeks of my patient, her immediate response to the message I just conveyed to her. Minutes before, with great angst anticipating the depressing effect my words will have on her, I proceeded to explain how her FSH was slightly elevated and her antral follicle count was a disappointing 3-6 follicles. I was careful to say that though this is a screen that correlates with a woman’s fertility, sometimes a woman may be more fertile than suspected based on the hormone tests and ovarian ultrasound. I also said that even when the tests accurately show diminishing ovarian reserve (follicle number), we are often successful in achieving a pregnancy and obtaining a baby through in vitro fertilization especially when age is not a significant factor.

These encounters I have with patients are more frequent than they should be. Unfortunately, many women delay seeking help in their efforts to conceive until their age has become significant both because they have fewer healthy genetically normal eggs and because their ability to respond to fertility drugs with numerous mature eggs is depressed. Women often do not realize that fertility drops as they age starting in their 20s but at an increasing rate in their 30s and to a point that may often be barely treatable in their 40s.

A common reason women delay seeking help is the trend in society to have children at an older age. In the 1960’s it was much less common that women would go to college and seek a career as is typical of women today. The delayed childbearing increases the exposure of women to more sexual partners and a consequent increased risk of developing pelvic inflammatory disease with resulting fallopian tube adhesions. When patients have endometriosis, delaying pregnancy allows the endometriosis to develop further and cause damage to a woman’s ovaries and fallopian tubes. They are more likely to develop diminished ovarian reserve at a younger age due to the destruction of normal ovarian tissue by the endometriosis. Even more important is that aging results in natural depletion of the number of follicles and eggs with an increase in the percentage of these residual eggs that are unhealthy and/or genetically abnormal.

Diminished ovarian reserve is associated with decreased inhibin levels which decreases the negative feedback on the pituitary gland. FSH produced by the pituitary is elevated in response to the diminished ovarian reserve and inhibin levels unless a woman has a cyst producing high estradiol levels which also lowers FSH. This is why we assess estradiol levels at the same time as FSH. Anti-Mullerian Hormone (AMH) can be tested throughout a woman’s menstrual cycle and levels correlate with ovarian reserve. Early follicular ultrasound can be performed to evaluate a woman’s antral follicle count. The antral follicle count also correlates with ovarian reserve.

By screening women annually with hormone tests and ultrasounds a physician may assess whether a woman is at high risk of developing diminished ovarian reserve in the subsequent year. Alerting a woman to her individual fertility status would allow women to adjust their family planning to fit their individual needs.

Aggressive fertility therapy may be the best option when it appears that one is running out of time. Ovulation induction with intrauterine insemination, MicroIVF and IVF are all considerations that speed up the process and allow a patient to take advantage of her residual fertility.

With fertility screening of day 3 estradiol and FSH, AMH and early follicular ultrasound antral follicle counts, the biological clock may still be ticking but at least one may keep an eye on it and know what time it is and act accordingly.

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TTC? Consider Clomid A First Step

By David Kreiner MD, and Tracey Minella

March 22nd, 2011 at 12:00 am


If doing IVF compares to swimming the English Channel, then Clomid is like dipping your toe in the water. You’ve got to get your feet wet somewhere when moving on from conceiving naturally to conceiving with medical assistance… and Clomid is that first step for many women.

Dr. David Kreiner of East Coast Fertility answers all your questions about Clomid therapy:

It has become commonplace for women who have been frustrated with repeated unsuccessful attempts to conceive naturally on their own to see their gynecologist who often times will try clomid therapy on them. Clomid, the traditional brand name for clomiphene citrate, is a competitive inhibitor of estrogen. It stimulates the pituitary gland to produce follicle stimulating hormone (FSH) which in turn will stimulate the ovaries to mature follicle(s) containing eggs. Estrogen normally has a negative effect on the pituitary: Clomid blocks estrogen and leads to pituitary FSH production and ovarian stimulation.

Infertility patients — those under 35 having one year and of unprotected intercourse without a resulting pregnancy and those over 35 having six months without pregnancy — have a two to five percent pregnancy rate each month trying on their own without treatment. Clomid therapy increases a couple’s fertility by increasing the number of eggs matured in a cycle and by producing a healthier egg and follicle. The pregnancy rate with clomid therapy alone is approximately ten percent per cycle and 12 -15 percent when combined with intrauterine insemination (IUI). Women who are unable to ovulate on their own experience a 20 percent pregnancy rate per cycle with clomid, the equivalent to that of a fertile couple trying on their own.

Clomid and Your Cervical Mucus

Women who are likely to conceive with clomid usually do so in the first three months of therapy, with very few conceiving after six months. As clomid has an anti-estrogen effect, the cervical mucus and endometrial lining may be adversely affected.

Cervical mucus is normally produced just prior to ovulation and may be noticed as a stringy egg white like discharge unique to the middle of a woman’s cycle just prior to and during ovulation. It provides the perfect environment for the sperm to swim through to gain access to a woman’s reproductive tract and find her egg. Unfortunately, clomid may thin out her cervical mucus, preventing the sperm’s entrance into her womb. IUI overcomes this issue through bypassing the cervical barrier and depositing the sperm directly into the uterus.

However, when the uterine lining or endometrium is affected by the anti-estrogic properties of clomid, an egg may be fertilized but implantation is unsuccessful due to the lack of secretory gland development in the uterus. The lining does not thicken as it normally would during the cycle. Attempts to overcome this problem with estrogen therapy are rarely successful.

Side Effects

Many women who take clomid experience no side effects. Others have complained of headache, mood changes, spots in front of their eyes, blurry vision, hot flashes and occasional cyst development (which normally resolves on its own). Most of these effects last no longer than the five or seven days that you take the clomid and have no permanent side effect. The incidence of twins is eight to ten percent with a one percent risk of triplet development.

Limit Your Clomid Cycles

Yet another deterrent to clomid use was a study performed years ago that suggested that women who used clomid for more than twelve cycles developed an increased incidence of ovarian tumors. It is therefore recommended by the American Society of Reproductive Medicine as well as the manufacturer of clomiphene that clomid be used for no more than six months after which it is recommended by both groups that patients proceed with treatment including gonadotropins (injectable hormones containing FSH and LH) to stimulate the ovaries in combination with intrauterine insemination or in vitro fertilization.

Success rates

For patients who fail to ovulate, clomid is successful in achieving a pregnancy in nearly 70 percent of cases. All other patients average close to a 50 percent pregnancy rate if they attempt six cycles with clomid, especially when they combine it with IUI. After six months, the success is less than five percent per month.

In vitro fertilization (IVF) is a successful alternative therapy when other pelvic factors such as tubal disease, tubal ligation, adhesions or scar tissue and endometriosis exist or there is a deficient number, volume or motility of sperm. Success rates with IVF are age, exam and history dependent. The average pregnancy rate with a single fresh IVF cycle is greater than 50 percent. For women under 35, the pregnancy rate for women after a single stimulation and retrieval is greater than 70 percent with a greater than 60 percent live birth rate at East Coast Fertility.

Young patients sometimes choose a minimal stimulation IVF or MicroIVF as an alternative to clomid/IUI cycles as a more successful and cost effective option as many of these patients experience a 40 percent pregnancy rate per retrieval at a cost today of about $3,900.

Today, with all these options available to patients, a woman desiring to build her family will usually succeed in becoming a mom.

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Journaling Your Infertility Journey

By Tracey Minella

January 11th, 2011 at 9:56 am

Your journey to the crib may be a short one. Or, it may be a long one. But if you are reading this, it’s already been longer than you thought.

If you’ve been trying to conceive for awhile and are ready to see (or already being treated by) a reproductive endocrinologist for specialized medical assistance getting pregnant, you need to get a journal. Today.

I don’t mean a simple calendar where you track everything from temperatures, period dates, FSH levels, retrieval, embryo, and cryo information, test results and important dates.

I’m talkin’ a good old-fashioned diary kind of journal.  The kind that you had back in the days when a zit on the night of the dance was your biggest problem. Back then, it had a little lock and key. And you wrote in it by hand…before keyboards replaced the pen. Long, heart-felt passages filled with teenage angst and emotion. Do you remember how it felt to unleash all those feelings on paper? How it helped relieve the stress you could barely contain?

Fast forward to today. Have you read that old diary recently? If not, go find it. Now. (I’ll wait…)

In those pages you’ll get a glimpse of the person you once were. A preview of the person you are today. And the memories and emotions of an important phase of your life will come flooding back in vivid detail. And you will laugh and cry and marvel at how you got through it all.

Right now, you may think you’ll remember all the painstaking details of all the poking and prodding, the tests and treatments, the surgeries and cycle specifics… for the rest of your life. But, trust me, you won’t. If all goes well, the space in your brain that memorized all the embryo details will be needed for new details… like when that long-awaited baby took its first step or said “Mama”.

Right now, you may even think that you’ll want to forget all of this drama. But I doubt it. This infertility journey, however long and painful it may get, will someday be another part of your history. It will shape the rest of your life. And if you don’t take the opportunity to record those stories and feelings now, as they are happening, they will be gone forever.

The journal of my seven year infertility journey killed a few trees. But in those pages, all the memories and emotions of an important phase of my life come flooding back in vivid detail. And I laugh and cry and marvel at how I got through it all.

This wild ride is so much bigger than a zit on the night of the dance.

Go get a pen and some paper. And while you’re at it, why not share some of your feelings right here?

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Over 40, and High FSH? What’s a Girl To Do?

By Dr. David Kreiner

August 20th, 2010 at 12:00 am

You have that dreaded infertility diagnosis, “Over 40 With High FSH Levels.” And there’s no cure or magic herb that will turn back the hands of time. You’re desperate so you are willing to try it all anyway, including acupuncture and some internet recommendations such as DHEA (dehydroepiendosterone).

You hear that you can lower your FSH with DHEA or estrogen. The fact is, however, elevated FSH levels do not cause a problem with conceiving. They are merely a marker of diminishing ovarian reserve, a depletion of ovarian follicles and eggs that, combined with increasing age, means you have very few genetically normal eggs available in your ovaries to achieve a healthy child.

Reproductive endocrinologists typically counsel “Over 40 With High FSH Levels” patients that their chance of successfully achieving a live birth using their own eggs is small and that by using a donated egg from a young, fertile woman they can increase their odds of giving birth to greater than 70 percent per donation. Unfortunately, this comes as a shocking disappointment to most women. It’s often a reason for them to drop out of a doctor’s practice or even quit trying to conceive.

So what do you do when faced with this situation? Your answer needs to be individualized, based on your emotional and financial resources, your motivation and your comfort with using a donated egg.

At our clinic, we try to come up with a strategy with our patients that includes counseling to begin the discussion about donor eggs, as opposed to trying with less chance for successful outcome using a patient’s own eggs, or stopping therapy completely and adopting or living child-free.

Perhaps you will choose a low tech option such as insemination with or without hormonal therapy. Sometimes, the plan will be to blast ahead with the big guns using IVF with full stimulation or with less medication and cost using MicroIVF or Minimal Stimulation IVF. Some patients respond better to different stimulations such as sensitizing with estrace or even DHEA prior to stimulation, using a lupron flare or even using clomid in combination with gonadotropins. Unfortunately, it is hard to predict what will be the optimal stimulation for you until we give it a shot.

The bottom line? There’s no right or wrong choice for you. Remember, a family can look many different ways and still be a healthy, loving unit. Your physician, nurses and counselors are available to assist you and support you with whatever decision you make.

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Ask The Doctor: “Do you think that women with a high FSH should try IVF one time with their own eggs?”

By Gregory Zapantis, M.d., Facog

August 2nd, 2010 at 12:00 am

Assuming a thorough fertility evaluation has been done and in-vitro fertilization (IVF) treatment is a potential option, IVF may or may not be recommended based on age or on ovarian reserve testing results.

A sharp decline in pregnancy rates with advancing female age is found with in-vitro fertilization.  The risk for miscarriage also progressively increases (1).  Above a certain age, the potential benefits of IVF disappear.  For instance, in a recent research review no clinical pregnancies resulted in women ≥45 years of age, and no deliveries resulted in women ≥44 years of age following IVF treatment (2).

Ovarian reserve describes a woman’s reproductive potential with regards to ovarian follicle number and egg quality.  Testing often used to determine ovarian reserve includes cycle day 2 or 3 FSH and estradiol hormone levels, or a clomiphene citrate challenge test. Specific abnormal values should be established by individual IVF centers based on their population.  Elevated FSH and estradiol values are independent predictors of poor prognosis with IVF.  FSH levels ≥10 mIU/mL and estradiol levels ≥80 pg/mL are often considered to be elevated.  However, cutoffs for FSH may be as high as 20-25 mIU/mL based on the FSH assay used, or on age.

Overall, though, no treatment other than egg donation has been shown to be effective for women over 40 and for those with compromised ovarian reserve.  IVF treatment in such cases, then, would be considered empiric.  Following proper counseling about the risks, benefits and alternatives of IVF, it may be reasonable to allow a couple to attempt an IVF cycle despite a high FSH level, so there are no future regrets about whether IVF should have been tried or not.  It should be noted that some IVF centers have exclusion criteria which do not permit IVF above certain day 2 or 3 FSH or estradiol levels.  Also, all IVF centers have a certain age threshold above which IVF using a woman’s own oocytes or eggs is not attempted.

References:

-ASRM Practice Committee Opinions: Aging and infertility in women.

-1) Smith KE, Buyalos RP. The profound impact of patient age on pregnancy outcome after early detection of fetal cardiac activity. Fertil Steril 1996;65:35-40.

-2) Ron-El R, Raziel A, Strassburger D, et. Al. Outcome of assisted reproductive techonology in women over the age of 41. Fertil Steril 2000;74:471-5.


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When You Can’t Conceive Again: The Pain of Secondary Infertility

By Dr. Allison Styne-gross

June 6th, 2010 at 6:00 pm

In this generation, a large percentage of my patients suffer from secondary infertility. Secondary infertility is defined as difficulty conceiving despite having successfully conceived and delivered a baby in the past. These patients often feel a lack of empathy from physicians, peers, and fellow patients with whom they share a waiting room (potentially for hours upon hours).  This lack of empathy has even been described as resentment — How could they be so upset or frustrated by the process when they already have a child? Taking my “doctor hat” off, as a mother of two, I can offer an explanation…

Every woman has a certain image of how they wish their lives to be. Some envision being married, some prefer to be single.  Some women envision having children, and some prefer to live without them. Whatever their dream may be, a woman will be determined to see it through.

After I conceived my daughter I started to realize that I had not yet fulfilled my own vision.  My original dream was to have at least one child. However, I grew up with a brother and once I had my one beautiful daughter, I realized the importance of providing her with the gift of a sibling. This now became the most important thing to me. I wanted to provide her with what I thought was this best gift of all. It became all that I thought about, and I was going to see to it that it happened.  I couldn’t imagine life without a sibling for her.  I finally did conceive again but this pregnancy ended in a loss. I was devastated. At this point, I started to fear that my dream was an impossibility. As an infertility specialist, I knew a little too much – this even worsened my fear. I knew that I was getting older.  I knew that my ovarian reserve would be declining, a common cause of secondary infertility. Was this the reason for my loss? Would I ever be able to conceive or are my ovaries too far gone? At this very time in my life, I was able to completely empathize with my patients. But especially with those who were suffering secondary infertility, those who felt shunned by all the other patients in the waiting room. I realized the importance of having a sibling for my daughter and of course it becomes more significant when it feels unattainable.

Fortunately, I did overcome this obstacle and had a second beautiful girl.  I am telling this story not only out of empathy, but also to provide some hope for those who suffer from secondary infertility.

There are many reasons why women suffer from secondary infertility. The most common being advanced reproductive age, tubal obstruction (from prior surgery, i.e. cesarean section or ectopic pregnancy), a worsening of a borderline male factor, endometriosis (which may have made the first time around more difficult but now seemingly impossible).  The beginning of every evaluation should include an evaluation of ovarian reserve. As women advance in maternal age, the ovaries may start to decline in function. With such a decline there can be an associated increased risk for chromosomal abnormalities leading to miscarriage. The evaluation of ovarian reserve includes a baseline ultrasound to assess the health of the ovary (looking for antral follicle number) and a blood test on day 3 of the menstrual cycle. The FSH and estradiol level included in the day 3 blood test is the most sensitive assessment that we currently have to screen ovarian reserve. 

The next step in the evaluation should include a hysterosalpingogram which is used to check for any intrauterine abnormalities that may affect implantation (i.e. polyps, fibroids, scar tissue) and to establish tubal patency. These are variables that may be compromised, especially following delivery via cesarean section or a pregnancy complicated by a peri-partum infection (endometritis, difficulty in removal of placenta, etc). Intrauterine pathologies and tubal obstruction are issues that can be corrected or bypassed and overcome. 

Reevaluation of the male partner is recommended because a borderline male factor can worsen with time.  Borderline sperm counts and endometriosis may make it more difficult to conceive so that it is not unusual that it took longer than expected to conceive the first time, and now it is more difficult to successfully achieve pregnancy the second time around.

Secondary infertility, like primary infertility, may be unexplained which, although not uncommon, is the most frustrating type of infertility to experience as a patient and physician. We all need a certain amount of control over our destiny and unexplained infertility relinquishes some of this control as we have no identifiable answers.  However, the good news is that there are several options for treatment including insemination with hormonal stimulation and if not successful, in vitro fertilization.

It is a long and emotionally draining process but taken from a doctor who has been through some ups and downs, it makes you a better person and a better mother.

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