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Archive for the ‘Estradiol’ 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.

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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.

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

 

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