viscousmemories
01-07-2007, 06:42 AM
Disclaimer: I am just an average Jane who found myself needing a crash course in human reproduction and complicated medical procedures. I have used layman’s terms and simplified explanations in this article, so may have some minor or unimportant technicality wrong, and if so please overlook it if the intended meaning is clear. If you find a glaring factual error, however, please notify me right away.
Infertility and A.R.T (Assisted Reproduction Technologies)
Even if you aren't dealing with infertility, chances are you know someone who is, has or will be, as it is estimated 15% of Americans trying to become pregnant experience infertility at some level. I know many people in my life want desperately to “be there” for me, and simply don’t have any frame of reference to fall back on in trying to help. I hope that this article helps you understand what an infertile couple is going through physically and emotionally so you can “be there” for your friend or loved one. If it turns out to be you in need of fertility treatments, maybe this will help you get started down the right path.
[B]Infertility in a Nutshell
Infertility is technically defined as having not achieved pregnancy after one year of unprotected intercourse. Many couples are dealing with secondary infertility, meaning they have had a child or children naturally, but are infertile now. Additionally, women who can conceive, but not carry to term due to recurrent pregnancy loss (miscarriages), or the loss/malfunction of the uterus, are considered infertile. Women trying to conceive without a partner, as well as same sex couples trying for a child are also represented in the infertile community. For ease of reference, I will use couples throughout the article, but the same treatments apply to all.
Conception
Because pregnancy is so commonplace, many people have little or no idea of all the factors involved in simple conception. This is easily understood because when something just works most of the time, we don’t feel the need to learn all about it. I have added this quick overview of conception as it is important to the infertility discussion to know what is supposed to happen.
All the eggs a woman will ever have are in her ovaries at birth, and the “cycle” these eggs undergo monthly is what drives reproduction. I will be using a single egg for illustration, but several eggs may be involved in any given month.
http://www.freethought-forum.com/images/ivf/repro1.jpgAt the beginning of the cycle, an egg begins to grow and undergo a chemical “maturation” in one of the two ovaries, forming its own little fluid filled chamber called an ovulatory follicle. At midcycle, a hormonal cue causes the follicle to “burst”, releasing the egg from the ovary where it finds its way into the fallopian tube. If sperm is present in the tube at this time, the egg may fertilize and become a zygote, and the zygote travels down the tube dividing and growing.
There are several stages from zygote to embryo, but for ease of reference I will use embryo from here forward. The embryo emerges into the uterus and starts secreting a protein as it rolls along the walls, which are lined with endometrium (tissue formed basically by blood, nutrients, and carbohydrates). This interplay between the embryo’s protein and the lining’s carbohydrates produces a “sticky” interaction and the embryo may eventually stop, chemically “burn” a hole into the endometrium and implant there. Pregnancy begins at implantation, not fertilization, as 50+% of embryos don’t implant at all and are simply flushed out with the unneeded endometrium during a woman’s period, the same way an unfertilized egg is.
Causes of Infertility
The first step in treatment is extensive testing to diagnose the cause. This diagnosis will indicate what treatment is most likely to be successful as with any medical problem. Some common causes include the following:
Male Factor (MFI): Problems with sperm such as low sperm count, high percentage of physically defective sperm, low sperm motility (swimmers don’t swim), previous vasectomy, and blockages causing sperm to be absent from the ejaculate even if they are produced in the testes.
Diminished ovarian reserve and “old eggs”: For the last several decades, many women have put off childbearing until reaching their mid thirties or even later, or are trying to start a second family or have a “change of life baby” after raising their previous children, not realizing that their fertility decreases every year. From Dr. Geoffrey Sher, a pioneer in IVF “Beyond the age of 35, each mature egg a woman produces is progressively less likely to be "normal," such that with every advancing year, fertilization of her eggs is more likely to produce embryos with abnormal chromosome number and/or structure” (source: www.haveababy.com). Abnormal eggs are much less likely to fertilize at all; natural selection.
Hormonal Factors: PCOS, or polycystic ovarian syndrome, in simple terms, is a hormonal imbalance characterized by too much testosterone in a woman’s body causing the follicles to not “burst” and instead swell bigger and bigger. This overload of testosterone causes problems with egg development and maturity as well and often there is a complete lack of ovulation. PCOS women additionally must often deal with obesity and insulin processing problems, which also affect fertility and the ability to carry. There are other hormonal issues leading to infertility, but PCOS is the most common.
Tubal Factor: A very common cause of infertility, and why IVF was developed, tubal disease is caused when the fallopian tubes are damaged and or blocked in some way and so eggs are unable to travel to the uterus. Partial blockages, which allow the egg and sperm to enter the tube, but not travel to the uterus, are the number one cause of ectopic or tubal pregnancies, which are very dangerous and can be fatal. Tubal blockages, called adhesions (scar tissue), may be caused by mechanical factors such as abdominal surgery, abortion and childbirth or from an infection such as Chlamydia. Fallopian tubes are very delicate and surgeries to remove adhesions often leave only a small window of time to try for a pregnancy before the scar tissue returns. Even then the chances of ectopic pregnancy are many times greater. Additionally, blocked tubes may fill with fluid and swell, called a hydrosalpinx. This fluid can leak into the uterine cavity and research indicates it is toxic to embryos.
http://www.freethought-forum.com/images/ivf/endo.jpgEndometriosis: A disease characterized by endometrial lining tissue growing in places other than the uterus such as on the ovaries, fallopian tubes, and even the abdominal wall (see diagram). This is a painful condition, and sufferers are sometimes incapacitated during part of their cycles as this lining grows and sheds. Endometriosis is also associated with toxins being found in the reproductive system as well as immunological problems causing implantation failure.
Ovulation problems: Some women simply don’t ovulate, or ovulate irregularly due to many factors including hormonal and genetic issues as well as ovarian malformation.
Unexplained: In about 5% of cases of infertility, the cause cannot be identified. This is especially difficult for the doctor and patient, as nobody knows what to address or what treatment to use. It is believed many of these unexplained cases have genetic problems with their eggs or sperm, and often donor gametes are recommended after failure of all other methods.
Recurrent pregnancy loss: Only recently have several researchers, namely Dr. Alan Beer (http://www.repro-med.net/) and Dr. Carolyn Coulam (http://www.haveababy.com/CITY.asp?site=chi) found that repeated miscarriages are often due to immunological issues in the mother. Their recommended treatments are still considered controversial and many doctors are calling them dangerous and refusing to study their findings. I know that both have had much success and that research is ongoing, so if you know someone with recurrent pregnancy loss, please at least let them know there are new treatments and aggressive and innovative doctors out there to help them.
[B]Emotional Affects of Infertility
Those dealing with infertility may feel confused, scared, depressed, ashamed and isolated. The ability to reproduce is perceived as a given, and is tied with one’s self esteem in many ways. Throughout history and across cultures, men have been considered strong only if they are virile and able to produce heirs, and “barren” women seen as something to be shunned, put aside, or even punished. An infertile couple may wonder what they did wrong that they are not “blessed”, may look at the ease with which “undeserving” people get pregnant and become bitter, may blame their spouse, may blame themselves.
Misguided and uninformed family, friends, and acquaintances often unknowingly add to the infertile person’s despair by making thoughtless comments. Below are some comments heard time and time again by those facing infertility, and should never be used if you really care and want to help rather than hurt. A good test of whether a platitude might be hurtful is to ask yourself, “Would I say this to a paraplegic?” I have posted how offensive it would sound to someone without the use of his or her legs, which is how an infertile person hears it. This is just a sampling; amongst the infertile, collecting and sharing these is a favorite pastime.
Just relax and you’ll get pregnant.
Just relax and you will walk.
Once you stop trying it will happen.
Once you stop trying, you will regain the use of your legs.
My <friend or relative> <drank/ate/used> <herbs/vitamins/juice/food/quack medicine> and got pregnant right away.
My sister was able to walk after drinking Aloe Vera/visiting a faith healer.
You should be glad you don’t have to deal with <unpleasant pregnancy symptom/bad child behavior>.
You should be glad you don’t have to deal with buying shoes/leg cramps/blisters.
Maybe you can’t get pregnant because you did something wrong <in this life/a past life/in the eyes of deity X>.
Maybe your paralysis is a punishment for living your life wrong.
Why don’t you just adopt?
Why don’t you just go buy some prosthetic legs?
About Adoption
I would like to make a further note on adoption as it is frequently mentioned in a myriad ways when some people learn you are infertile. Especially common is the one above, where the word “just” is used to indicate that adoption is the simplest and easiest solution. This is not a process where the word “just” is accurate. Adoption is very expensive, highly stressful, and competitive, and though a valid family building choice, is not for everyone. Most infertile couples would like to try for their own biological child, or try to experience pregnancy, childbirth, and breastfeeding even if using donated gametes or embryos, before researching adoption.
[B]Resources and Further Information
General Information
The Sher Institute of Reproductive Medicine (http://www.haveababy.com) is the clinic I chose after years of research. Dr. Sher is a pioneer in the field of infertility; he opened the first private IVF program in the country and developed many protocols and procedures that are now standard practice. He is active in the fights for useful, accurate statistical reporting and mandated insurance coverage for infertility.
His hand-picked associate doctors have impressive resumes themselves. SIRM has a discussion board and the doctors will answer questions from anyone, not just their own patients, and several of them post on various support boards as well. SIRM offers free consultations whereas most “top tier” clinics charge $500.00 or more. Considered a maverick, Dr. Sher is quick to discard old ways of doing things and explore new territory.
Resolve:The National Infertility Association (http://www.resolve.org) is a great site for information, activism and advocacy. I do not recommend their message board, however.
Peer Support
IVF Connections (http://www.ivfconnections.com): a huge site with discussion boards (http://www.ivfconnections.com/board/index.php) broken down by state, diagnosis, age, stage in treatment, dealing with stress, and even pregnancy and baby names. You can also form cycle buddy groups to interact with those going through the same procedure at around the same time.
Ovusoft (http://www.ovusoft.com) is centered around fertility tracking software and includes sections on dealing with infertility, endometriosis, and PCOS
The next installment will contain information on Assisted Reproduction Techniques as well as a discussion of ethical, emotional and financial considerations.
[B]Considerations
Almost every infertile woman has heard the words "There is nothing more I can do for you, you need to see a fertility specialist" from her regular gynecologist. These are difficult words to hear and process as a hope has just been shattered and a new and unknown world entered, one full of strange acronyms and scary concepts. Sharing this news with one’s partner is especially difficult, and anecdotally, men seem far more reluctant to take that next step.
When it is time to move on to specialized treatment, some considerations are:
Where do we go?
Infertility is big business as well as high tech medicine. Clinics and REs (Reproductive Endocrinologists, or fertility specialists) are in constant competition to be the "best" to the point where some fudge their success rate statistics, criticize or flat out misrepresent other REs and programs, and refuse to treat "tough" cases. Others face the competition more positively by superspecializing (for example, a clinic might build a reputation as "the place for women over 40"), being cutting edge and innovating new treatments and procedures, offering creative financing options, and providing personalized, caring service. Something as seemingly inconsequential as whether the RE does routine ultrasounds personally or has a technician do them can be a make or break point in this industry.
Some couples rely on the suggestions of friends, family members, their gynecologists, strangers on infertility support boards, or simply choose the closest clinic. Most, however, at least try to do the research and get the best they can afford, which is a monumental and frustrating task. Wading through the CDC stats (http://www.cdc.gov/reproductivehealth/art.htm) is likely to lead to more questions than answers because so many variables aren’t included in them.
To help narrow it down for anyone reading this, the three top clinics in the US, traditionally, are St. Barnabus, Cornell, and CCRM (Colorado Center for Reproductive Medicine). Also in the top tier are SIRM (Sher Institute of Reproductive Medicine) and NYU. There are other excellent local and regional programs, but many couples choose to travel to one of the top clinics to give themselves the best chance at success.
How will we pay?
At this point, many couples will find out that their insurance doesn't cover any treatment for infertility or testing at all, or is very limited, and will need to carefully review their finances. Even an initial consultation, in person or via telephone, with a top clinic can cost $500.00, and that’s just to see if they will take you.
The consultation is necessary however, as is testing, so a course of treatment can be mapped out. Some clinics are able to push testing through insurance; others are pay as you go. Some clinics offer IVF or IUI "packages", aka shared risk (meaning you can receive a partial or complete refund if pregnancy is not achieved). Others are fee for service regardless of the outcome. The average cost for a single IVF cycle, including medications, is 11-14 thousand dollars. At this point, many couples will pay for testing and diagnosis, then work to save or borrow whatever amount they need to continue.
How far are we willing to go? What are we willing to do?
Couples must also consider their personal, religious, and ethical positions with regards to assisted reproduction. Some religions forbid certain courses of treatment while others allow them under strict guidelines while still others don’t address infertility at all. Many couples find themselves weighing their desire for a family against their religious beliefs, which can be extremely stressful. Friends and family members may believe it is wrong to interfere with Mother Nature or God and will not support you. You may have a strong belief that an individual, human life begins at conception and have to consider the possibility that you may end up with extra embryos…are you willing to cryopreserve them? Donate them to other couples? Allow them to be destroyed? Many embryos are lost during the process either in the lab or in your body. Can you cope with those losses?
Couples should also set realistic limits for their treatment, but remain somewhat flexible. How many cycles of drugs are you willing to do before moving on to IUI? How many IUIs before IVF? How long will you stay with your RE before getting a second opinion if you aren't successful? How much can you afford? Are you willing to say, at some point, "We have done all we can" and give up on treatment? Will you then move on to adoption or choose to be childfree?
None of these limits should be set in stone, but having a plan of some sort should treatment fail can reduce stress, marital discord, and depression. Once the clinic is chosen, the diagnosis made, course of treatment determined, personal values considered, limits discussed and finances arranged the treatment - and the real stress - can begin.
[B]A.R.T.
Assisted reproductive technologies were developed to allow infertile couples to bypass whatever obstacle they are encountering and achieve pregnancy and includes everything from oral and injectible drugs to high tech "test tube babies" or IVF. Depending on the cause of the infertility, a couple may progressively move up this ladder of complexity, undergoing several types of treatments.
In the not so distant past, many of these treatments were new and unrefined, leading to headline garnering high order multiple births. Today, ethical clinics and doctors closely monitor their patients and any more than triplets is very rare and viewed negatively by the infertile community as a whole.
A.R.T includes, but is not limited to, the following:
Ovulation inducing drugs: If the diagnosis is ovulation problems, an oral drug called Clomid is often the first treatment. Clomid slightly stimulates the ovaries without over stimulating them, causing them to produce two or three ovulatory follicles. Ovulation can be predicted in one of several ways (ovulation predictor test or ultrasound monitoring) and timed intercourse prescribed. There are other stimulation drugs but Clomid seems to be a "first line" treatment.
http://www.lasvegasfertility.net/iui.jpg
IUI diagram
IUI: Intra uterine insemination is sometimes called artificial insemination. During an IUI cycle, the semen is collected and all the seminal fluid removed leaving only the sperm, then the sperm are introduced directly to the uterus via a catheter inserted through the cervix. IUIs may be done in conjunction with drugs to increase ovarian production, or naturally upon ovulation. Sometimes two IUIs are done a few days apart just before and just after the predicted ovulation date to maximize chance of success. Ovulation can also be induced with a hormone called HCG, allowing more precise timing.
IUI is indicated when infertility is caused by some kind of problem with the sperm reaching the uterus and fallopian tubes, such as hostile cervical mucous that destroys the sperm, or low motility where the sperm cannot swim to where they need to be.
Unfortunately, IUI is often the only procedure covered by insurance, or all the couple can afford, and so is used in cases where it is not necessarily indicated, leading to multiple failures. Success rates with IUI peak on the 4th round then decline rapidly.
IVF: In vitro fertilization (literally meaning "in glass") is the grand high poobah of assisted reproduction technologies. IVF was originally developed to bypass blocked or damaged fallopian tubes, but is used with many other diagnoses today and offers the highest success rates of all treatments. IVF is a process, not an event, and involves the following:
Suppression, stimulation, and support drugs - IVF is expensive and time consuming, so more than one egg is desirable, http://www.475-baby.com/img/progeny/2.jpg
Follicles as seen under ultrasound
and most women will undergo controlled hyperstimulation of the ovaries. This involves suppressing the natural ovulatory hormonal cycle, then stimulating the ovaries to produce numerous follicles/eggs, and collecting or retrieving the eggs before they are lost to ovulation.
This is achieved using various drug regimens, called protocols, and women undergoing IVF will self inject these drugs. Support drugs are used to create a good environment for the embryos, prevent rejection, and prevent infection and include folic acid, oral antibiotics and steroids and injectible hormones. You can read more about commonly used drugs here (http://www.haveababy.com/infert/drugs.asp).
Egg retrieval - Once the ovaries have produced a number of follicles http://www.475-baby.com/img/progeny/7.jpg
ICSI - anywhere from 8-30 depending on the patient’s response to stimulation - the doctor will retrieve them. The patient is generally put under light anesthesia and a needle is inserted through the vaginal wall into the ovaries, guided ultrasonically. The contents of each follicle, usually containing one egg, are then aspirated and the contents of the needle given to the embryologist.
Fertilization - While the woman is having her eggs retrieved; the man produces a sperm sample, which is also given to the embryologist to use to fertilize the retrieved eggs. Labs vary greatly and this process can involve simply introducing all the eggs and sperm into one petri dish to fertilize naturally or injecting each egg individually with a single sperm, chosen by the embryologist, in a procedure called ICSI or Intracytoplasmic Sperm Injection. Some eggs will not fertilize at all due to abnormalities, immaturity, or other factors.
Embryo culture - The fertilized eggs are then transferred http://www.med.utah.edu/andrology/images/clinical_services/level_1_embryo.jpg
Embryoto a growth medium. Again, labs vary and some culture all embryos in a single dish while others separate them and culture them individually. The usual culture time is 3 days, but in some cases this is extended to 5 days, or blastocyst stage. There is some debate on the risks versus benefits of blastocyst transfers, and studies being done, which you can read about at the links in the resources section. Embryos may arrest at any time during the culture due to quality factors with the egg or sperm and/or problems with the culture media or lab procedures. At the end of the culture cycle, the embryos are graded on a number of criteria including growth rate, symmetry, and number of cells.
If indicated by the patient’s medical history, a single cell may be removed from each embryo and tested for genetic abnormalities called PGD or Preimplantation Genetic Diagnosis. This allows the doctor to choose normal embryos for transfer. The embryo’s gender can also be determined during PGD, but as there is some risk to the embryo with this procedure, gender identification is rarely the motivation behind it and no reputable clinics I have heard of will do this for gender choice alone. Even if gender choice were advertised, IVF is expensive, painful, and under perfect circumstances only has a 50% success rate, so I doubt many people would undergo it just for gender choice purposes.
Embryo Transfer - The doctor and patient will go over the embryo reports and decide how many embryos to transfer to the woman’s uterus. The average in the US is three. More may be transferred under certain circumstances, but only if high order multiples is very unlikely. The transfer itself is a simple procedure; a catheter is inserted through the woman’s cervix into her uterus and the embryos transferred with a small amount of the culture media. Placement is important so this procedure is done under ultrasonic guidance.
Support, monitoring and follow-up - After transfer, the patient will take pregnancy support drugs, like progesterone, which is usually self administered as an intramuscular injection, but suppositories and intravaginal gels are also used. A pregnancy test, called a beta blood HCG test or “beta” for short, is given anywhere from 8-14 days post transfer. Amongst people undergoing IVF, this time period is called the 2-week wait (2WW on message boards) and is considered the worst part of the whole process.
If the first beta is positive (what constitutes a positive depends on the day post transfer and the clinic), a second test will be done 2 days later. In a healthy early pregnancy, this number will approximately double every 48 hours, confirming the positive. Sometimes, the embryos will implant, producing a positive beta, then fail or disappear before the second beta. This is called a chemical pregnancy and is very common.
An ultrasound is usually performed at about 5 weeks post egg retrieval to determine the pregnancy is within normal growth parameters, and to see if multiple gestation sacs are present. Two weeks later, at 7 weeks post retrieval; another ultrasound is performed specifically looking for a heartbeat. If a heartbeat is detected, the chance of miscarriage drops to 2% from 30%, and the patient can be released to her regular obstetrician.
ZIFT and GIFT: These two procedures are not as common as IVF, but still may be indicated depending on the diagnosis. The thinking behind them is that it’s best for things to happen within the body as much as possible.
GIFT stands for gamete intrafallopian transfer. In this procedure, a woman’s ovaries are stimulated with drugs to produce a number of eggs, the eggs are retrieved, mixed with processed sperm, and the resulting mixture placed in the fallopian tubes under laparoscopic guidance. Fertilization then may happen naturally within the tube.
ZIFT stands for zygote intrafallopian transfer. This procedure involves elements from both IVF and GIFT. The ovaries are stimulated and eggs retrieved, then the eggs are fertilized in vitro. The fertilized eggs (zygotes) are then transferred to the fallopian tubes under laparoscopic guidance to divide and grow and travel to the uterus.
[B]The Roller Coaster
In closing, I would like to discuss the physical and emotional aspects of IVF treatment from my personal experience, so you may support a loved one, or prepare yourself.
The drugs mimic the symptoms of menopause, PMS, and pregnancy respectively, while magnifying them in intensity and condensing them into a single month. The side effects can be overwhelming to some women and barely noticed by others.
Egg retrieval is a minor surgery involving recovery from anesthesia and trauma. Do not expect to bounce back immediately.
In almost all phases, there is no place for modesty or sexual privacy. You may be spread eagle in the stirrups with no covering while technicians and nurses walk in and out. Men, you will be given a cup and told to go to "the room" where everyone knows what you are doing and touching the "reading materials" is ill advised. You may be prescribed sex and have it written on a calendar or instruction sheet. You will be asked questions about cervical mucus and bowel habits and sexual positions. If you are a shy, private person, I suggest you find a way to cope with this BEFORE being subjected to it.
You may find yourself resenting each other, or laying blame on your significant other if he or she is the “infertile” one, or blaming yourself and taking it out on your partner. Please keep the lines of communication open, be understanding and forgiving, and try to face this as a team; many couples have broken up over infertility because they couldn’t stand the strain.
In short, please try to empathize with your loved one (and yourselves for that matter) who may be exhausted, bloated, broken out, in pain, experiencing a host of gastrointestinal problems, ashamed, and overly emotional as well as anxiety ridden about the outcome.
[B]Resources
Rhonda Levy (http://www.rhondalevy.com/choosingclinics.htm) will give you her claimed exhaustive research and the names of the top clinics in the US for a consultation fee, but I have no idea how accurate or helpful her information is.
Betabase Info (http://www.betabase.info): a couple undergoing IVF and seeing how women obsess over their beta numbers and doubling times created a self reporting database to show the huge variances
Three day versus blastocyst transfer debate:
Article from Haveababy (http://www.haveababy.com/infert/day3vday5.asp?site=)
Article from INCIID (http://www.inciid.org/asrm/day5or3.html)
Article from Advanced Fertility (http://www.advancedfertility.com/blastocystpregnancyrates.htm)
Empty Arms (http://www.vocalicious.com/empty_arms) A beautiful flash movie about infertility designed by Zuzu at Ovusoft Forums.
Book: In Vitro Fertilization: The A.R.T. of Making Babies (http://www.infertilitybooks.com/titles/in_vitro_fertilization_art_making_babies.html)
Infertility and A.R.T (Assisted Reproduction Technologies)
Even if you aren't dealing with infertility, chances are you know someone who is, has or will be, as it is estimated 15% of Americans trying to become pregnant experience infertility at some level. I know many people in my life want desperately to “be there” for me, and simply don’t have any frame of reference to fall back on in trying to help. I hope that this article helps you understand what an infertile couple is going through physically and emotionally so you can “be there” for your friend or loved one. If it turns out to be you in need of fertility treatments, maybe this will help you get started down the right path.
[B]Infertility in a Nutshell
Infertility is technically defined as having not achieved pregnancy after one year of unprotected intercourse. Many couples are dealing with secondary infertility, meaning they have had a child or children naturally, but are infertile now. Additionally, women who can conceive, but not carry to term due to recurrent pregnancy loss (miscarriages), or the loss/malfunction of the uterus, are considered infertile. Women trying to conceive without a partner, as well as same sex couples trying for a child are also represented in the infertile community. For ease of reference, I will use couples throughout the article, but the same treatments apply to all.
Conception
Because pregnancy is so commonplace, many people have little or no idea of all the factors involved in simple conception. This is easily understood because when something just works most of the time, we don’t feel the need to learn all about it. I have added this quick overview of conception as it is important to the infertility discussion to know what is supposed to happen.
All the eggs a woman will ever have are in her ovaries at birth, and the “cycle” these eggs undergo monthly is what drives reproduction. I will be using a single egg for illustration, but several eggs may be involved in any given month.
http://www.freethought-forum.com/images/ivf/repro1.jpgAt the beginning of the cycle, an egg begins to grow and undergo a chemical “maturation” in one of the two ovaries, forming its own little fluid filled chamber called an ovulatory follicle. At midcycle, a hormonal cue causes the follicle to “burst”, releasing the egg from the ovary where it finds its way into the fallopian tube. If sperm is present in the tube at this time, the egg may fertilize and become a zygote, and the zygote travels down the tube dividing and growing.
There are several stages from zygote to embryo, but for ease of reference I will use embryo from here forward. The embryo emerges into the uterus and starts secreting a protein as it rolls along the walls, which are lined with endometrium (tissue formed basically by blood, nutrients, and carbohydrates). This interplay between the embryo’s protein and the lining’s carbohydrates produces a “sticky” interaction and the embryo may eventually stop, chemically “burn” a hole into the endometrium and implant there. Pregnancy begins at implantation, not fertilization, as 50+% of embryos don’t implant at all and are simply flushed out with the unneeded endometrium during a woman’s period, the same way an unfertilized egg is.
Causes of Infertility
The first step in treatment is extensive testing to diagnose the cause. This diagnosis will indicate what treatment is most likely to be successful as with any medical problem. Some common causes include the following:
Male Factor (MFI): Problems with sperm such as low sperm count, high percentage of physically defective sperm, low sperm motility (swimmers don’t swim), previous vasectomy, and blockages causing sperm to be absent from the ejaculate even if they are produced in the testes.
Diminished ovarian reserve and “old eggs”: For the last several decades, many women have put off childbearing until reaching their mid thirties or even later, or are trying to start a second family or have a “change of life baby” after raising their previous children, not realizing that their fertility decreases every year. From Dr. Geoffrey Sher, a pioneer in IVF “Beyond the age of 35, each mature egg a woman produces is progressively less likely to be "normal," such that with every advancing year, fertilization of her eggs is more likely to produce embryos with abnormal chromosome number and/or structure” (source: www.haveababy.com). Abnormal eggs are much less likely to fertilize at all; natural selection.
Hormonal Factors: PCOS, or polycystic ovarian syndrome, in simple terms, is a hormonal imbalance characterized by too much testosterone in a woman’s body causing the follicles to not “burst” and instead swell bigger and bigger. This overload of testosterone causes problems with egg development and maturity as well and often there is a complete lack of ovulation. PCOS women additionally must often deal with obesity and insulin processing problems, which also affect fertility and the ability to carry. There are other hormonal issues leading to infertility, but PCOS is the most common.
Tubal Factor: A very common cause of infertility, and why IVF was developed, tubal disease is caused when the fallopian tubes are damaged and or blocked in some way and so eggs are unable to travel to the uterus. Partial blockages, which allow the egg and sperm to enter the tube, but not travel to the uterus, are the number one cause of ectopic or tubal pregnancies, which are very dangerous and can be fatal. Tubal blockages, called adhesions (scar tissue), may be caused by mechanical factors such as abdominal surgery, abortion and childbirth or from an infection such as Chlamydia. Fallopian tubes are very delicate and surgeries to remove adhesions often leave only a small window of time to try for a pregnancy before the scar tissue returns. Even then the chances of ectopic pregnancy are many times greater. Additionally, blocked tubes may fill with fluid and swell, called a hydrosalpinx. This fluid can leak into the uterine cavity and research indicates it is toxic to embryos.
http://www.freethought-forum.com/images/ivf/endo.jpgEndometriosis: A disease characterized by endometrial lining tissue growing in places other than the uterus such as on the ovaries, fallopian tubes, and even the abdominal wall (see diagram). This is a painful condition, and sufferers are sometimes incapacitated during part of their cycles as this lining grows and sheds. Endometriosis is also associated with toxins being found in the reproductive system as well as immunological problems causing implantation failure.
Ovulation problems: Some women simply don’t ovulate, or ovulate irregularly due to many factors including hormonal and genetic issues as well as ovarian malformation.
Unexplained: In about 5% of cases of infertility, the cause cannot be identified. This is especially difficult for the doctor and patient, as nobody knows what to address or what treatment to use. It is believed many of these unexplained cases have genetic problems with their eggs or sperm, and often donor gametes are recommended after failure of all other methods.
Recurrent pregnancy loss: Only recently have several researchers, namely Dr. Alan Beer (http://www.repro-med.net/) and Dr. Carolyn Coulam (http://www.haveababy.com/CITY.asp?site=chi) found that repeated miscarriages are often due to immunological issues in the mother. Their recommended treatments are still considered controversial and many doctors are calling them dangerous and refusing to study their findings. I know that both have had much success and that research is ongoing, so if you know someone with recurrent pregnancy loss, please at least let them know there are new treatments and aggressive and innovative doctors out there to help them.
[B]Emotional Affects of Infertility
Those dealing with infertility may feel confused, scared, depressed, ashamed and isolated. The ability to reproduce is perceived as a given, and is tied with one’s self esteem in many ways. Throughout history and across cultures, men have been considered strong only if they are virile and able to produce heirs, and “barren” women seen as something to be shunned, put aside, or even punished. An infertile couple may wonder what they did wrong that they are not “blessed”, may look at the ease with which “undeserving” people get pregnant and become bitter, may blame their spouse, may blame themselves.
Misguided and uninformed family, friends, and acquaintances often unknowingly add to the infertile person’s despair by making thoughtless comments. Below are some comments heard time and time again by those facing infertility, and should never be used if you really care and want to help rather than hurt. A good test of whether a platitude might be hurtful is to ask yourself, “Would I say this to a paraplegic?” I have posted how offensive it would sound to someone without the use of his or her legs, which is how an infertile person hears it. This is just a sampling; amongst the infertile, collecting and sharing these is a favorite pastime.
Just relax and you’ll get pregnant.
Just relax and you will walk.
Once you stop trying it will happen.
Once you stop trying, you will regain the use of your legs.
My <friend or relative> <drank/ate/used> <herbs/vitamins/juice/food/quack medicine> and got pregnant right away.
My sister was able to walk after drinking Aloe Vera/visiting a faith healer.
You should be glad you don’t have to deal with <unpleasant pregnancy symptom/bad child behavior>.
You should be glad you don’t have to deal with buying shoes/leg cramps/blisters.
Maybe you can’t get pregnant because you did something wrong <in this life/a past life/in the eyes of deity X>.
Maybe your paralysis is a punishment for living your life wrong.
Why don’t you just adopt?
Why don’t you just go buy some prosthetic legs?
About Adoption
I would like to make a further note on adoption as it is frequently mentioned in a myriad ways when some people learn you are infertile. Especially common is the one above, where the word “just” is used to indicate that adoption is the simplest and easiest solution. This is not a process where the word “just” is accurate. Adoption is very expensive, highly stressful, and competitive, and though a valid family building choice, is not for everyone. Most infertile couples would like to try for their own biological child, or try to experience pregnancy, childbirth, and breastfeeding even if using donated gametes or embryos, before researching adoption.
[B]Resources and Further Information
General Information
The Sher Institute of Reproductive Medicine (http://www.haveababy.com) is the clinic I chose after years of research. Dr. Sher is a pioneer in the field of infertility; he opened the first private IVF program in the country and developed many protocols and procedures that are now standard practice. He is active in the fights for useful, accurate statistical reporting and mandated insurance coverage for infertility.
His hand-picked associate doctors have impressive resumes themselves. SIRM has a discussion board and the doctors will answer questions from anyone, not just their own patients, and several of them post on various support boards as well. SIRM offers free consultations whereas most “top tier” clinics charge $500.00 or more. Considered a maverick, Dr. Sher is quick to discard old ways of doing things and explore new territory.
Resolve:The National Infertility Association (http://www.resolve.org) is a great site for information, activism and advocacy. I do not recommend their message board, however.
Peer Support
IVF Connections (http://www.ivfconnections.com): a huge site with discussion boards (http://www.ivfconnections.com/board/index.php) broken down by state, diagnosis, age, stage in treatment, dealing with stress, and even pregnancy and baby names. You can also form cycle buddy groups to interact with those going through the same procedure at around the same time.
Ovusoft (http://www.ovusoft.com) is centered around fertility tracking software and includes sections on dealing with infertility, endometriosis, and PCOS
The next installment will contain information on Assisted Reproduction Techniques as well as a discussion of ethical, emotional and financial considerations.
[B]Considerations
Almost every infertile woman has heard the words "There is nothing more I can do for you, you need to see a fertility specialist" from her regular gynecologist. These are difficult words to hear and process as a hope has just been shattered and a new and unknown world entered, one full of strange acronyms and scary concepts. Sharing this news with one’s partner is especially difficult, and anecdotally, men seem far more reluctant to take that next step.
When it is time to move on to specialized treatment, some considerations are:
Where do we go?
Infertility is big business as well as high tech medicine. Clinics and REs (Reproductive Endocrinologists, or fertility specialists) are in constant competition to be the "best" to the point where some fudge their success rate statistics, criticize or flat out misrepresent other REs and programs, and refuse to treat "tough" cases. Others face the competition more positively by superspecializing (for example, a clinic might build a reputation as "the place for women over 40"), being cutting edge and innovating new treatments and procedures, offering creative financing options, and providing personalized, caring service. Something as seemingly inconsequential as whether the RE does routine ultrasounds personally or has a technician do them can be a make or break point in this industry.
Some couples rely on the suggestions of friends, family members, their gynecologists, strangers on infertility support boards, or simply choose the closest clinic. Most, however, at least try to do the research and get the best they can afford, which is a monumental and frustrating task. Wading through the CDC stats (http://www.cdc.gov/reproductivehealth/art.htm) is likely to lead to more questions than answers because so many variables aren’t included in them.
To help narrow it down for anyone reading this, the three top clinics in the US, traditionally, are St. Barnabus, Cornell, and CCRM (Colorado Center for Reproductive Medicine). Also in the top tier are SIRM (Sher Institute of Reproductive Medicine) and NYU. There are other excellent local and regional programs, but many couples choose to travel to one of the top clinics to give themselves the best chance at success.
How will we pay?
At this point, many couples will find out that their insurance doesn't cover any treatment for infertility or testing at all, or is very limited, and will need to carefully review their finances. Even an initial consultation, in person or via telephone, with a top clinic can cost $500.00, and that’s just to see if they will take you.
The consultation is necessary however, as is testing, so a course of treatment can be mapped out. Some clinics are able to push testing through insurance; others are pay as you go. Some clinics offer IVF or IUI "packages", aka shared risk (meaning you can receive a partial or complete refund if pregnancy is not achieved). Others are fee for service regardless of the outcome. The average cost for a single IVF cycle, including medications, is 11-14 thousand dollars. At this point, many couples will pay for testing and diagnosis, then work to save or borrow whatever amount they need to continue.
How far are we willing to go? What are we willing to do?
Couples must also consider their personal, religious, and ethical positions with regards to assisted reproduction. Some religions forbid certain courses of treatment while others allow them under strict guidelines while still others don’t address infertility at all. Many couples find themselves weighing their desire for a family against their religious beliefs, which can be extremely stressful. Friends and family members may believe it is wrong to interfere with Mother Nature or God and will not support you. You may have a strong belief that an individual, human life begins at conception and have to consider the possibility that you may end up with extra embryos…are you willing to cryopreserve them? Donate them to other couples? Allow them to be destroyed? Many embryos are lost during the process either in the lab or in your body. Can you cope with those losses?
Couples should also set realistic limits for their treatment, but remain somewhat flexible. How many cycles of drugs are you willing to do before moving on to IUI? How many IUIs before IVF? How long will you stay with your RE before getting a second opinion if you aren't successful? How much can you afford? Are you willing to say, at some point, "We have done all we can" and give up on treatment? Will you then move on to adoption or choose to be childfree?
None of these limits should be set in stone, but having a plan of some sort should treatment fail can reduce stress, marital discord, and depression. Once the clinic is chosen, the diagnosis made, course of treatment determined, personal values considered, limits discussed and finances arranged the treatment - and the real stress - can begin.
[B]A.R.T.
Assisted reproductive technologies were developed to allow infertile couples to bypass whatever obstacle they are encountering and achieve pregnancy and includes everything from oral and injectible drugs to high tech "test tube babies" or IVF. Depending on the cause of the infertility, a couple may progressively move up this ladder of complexity, undergoing several types of treatments.
In the not so distant past, many of these treatments were new and unrefined, leading to headline garnering high order multiple births. Today, ethical clinics and doctors closely monitor their patients and any more than triplets is very rare and viewed negatively by the infertile community as a whole.
A.R.T includes, but is not limited to, the following:
Ovulation inducing drugs: If the diagnosis is ovulation problems, an oral drug called Clomid is often the first treatment. Clomid slightly stimulates the ovaries without over stimulating them, causing them to produce two or three ovulatory follicles. Ovulation can be predicted in one of several ways (ovulation predictor test or ultrasound monitoring) and timed intercourse prescribed. There are other stimulation drugs but Clomid seems to be a "first line" treatment.
http://www.lasvegasfertility.net/iui.jpg
IUI diagram
IUI: Intra uterine insemination is sometimes called artificial insemination. During an IUI cycle, the semen is collected and all the seminal fluid removed leaving only the sperm, then the sperm are introduced directly to the uterus via a catheter inserted through the cervix. IUIs may be done in conjunction with drugs to increase ovarian production, or naturally upon ovulation. Sometimes two IUIs are done a few days apart just before and just after the predicted ovulation date to maximize chance of success. Ovulation can also be induced with a hormone called HCG, allowing more precise timing.
IUI is indicated when infertility is caused by some kind of problem with the sperm reaching the uterus and fallopian tubes, such as hostile cervical mucous that destroys the sperm, or low motility where the sperm cannot swim to where they need to be.
Unfortunately, IUI is often the only procedure covered by insurance, or all the couple can afford, and so is used in cases where it is not necessarily indicated, leading to multiple failures. Success rates with IUI peak on the 4th round then decline rapidly.
IVF: In vitro fertilization (literally meaning "in glass") is the grand high poobah of assisted reproduction technologies. IVF was originally developed to bypass blocked or damaged fallopian tubes, but is used with many other diagnoses today and offers the highest success rates of all treatments. IVF is a process, not an event, and involves the following:
Suppression, stimulation, and support drugs - IVF is expensive and time consuming, so more than one egg is desirable, http://www.475-baby.com/img/progeny/2.jpg
Follicles as seen under ultrasound
and most women will undergo controlled hyperstimulation of the ovaries. This involves suppressing the natural ovulatory hormonal cycle, then stimulating the ovaries to produce numerous follicles/eggs, and collecting or retrieving the eggs before they are lost to ovulation.
This is achieved using various drug regimens, called protocols, and women undergoing IVF will self inject these drugs. Support drugs are used to create a good environment for the embryos, prevent rejection, and prevent infection and include folic acid, oral antibiotics and steroids and injectible hormones. You can read more about commonly used drugs here (http://www.haveababy.com/infert/drugs.asp).
Egg retrieval - Once the ovaries have produced a number of follicles http://www.475-baby.com/img/progeny/7.jpg
ICSI - anywhere from 8-30 depending on the patient’s response to stimulation - the doctor will retrieve them. The patient is generally put under light anesthesia and a needle is inserted through the vaginal wall into the ovaries, guided ultrasonically. The contents of each follicle, usually containing one egg, are then aspirated and the contents of the needle given to the embryologist.
Fertilization - While the woman is having her eggs retrieved; the man produces a sperm sample, which is also given to the embryologist to use to fertilize the retrieved eggs. Labs vary greatly and this process can involve simply introducing all the eggs and sperm into one petri dish to fertilize naturally or injecting each egg individually with a single sperm, chosen by the embryologist, in a procedure called ICSI or Intracytoplasmic Sperm Injection. Some eggs will not fertilize at all due to abnormalities, immaturity, or other factors.
Embryo culture - The fertilized eggs are then transferred http://www.med.utah.edu/andrology/images/clinical_services/level_1_embryo.jpg
Embryoto a growth medium. Again, labs vary and some culture all embryos in a single dish while others separate them and culture them individually. The usual culture time is 3 days, but in some cases this is extended to 5 days, or blastocyst stage. There is some debate on the risks versus benefits of blastocyst transfers, and studies being done, which you can read about at the links in the resources section. Embryos may arrest at any time during the culture due to quality factors with the egg or sperm and/or problems with the culture media or lab procedures. At the end of the culture cycle, the embryos are graded on a number of criteria including growth rate, symmetry, and number of cells.
If indicated by the patient’s medical history, a single cell may be removed from each embryo and tested for genetic abnormalities called PGD or Preimplantation Genetic Diagnosis. This allows the doctor to choose normal embryos for transfer. The embryo’s gender can also be determined during PGD, but as there is some risk to the embryo with this procedure, gender identification is rarely the motivation behind it and no reputable clinics I have heard of will do this for gender choice alone. Even if gender choice were advertised, IVF is expensive, painful, and under perfect circumstances only has a 50% success rate, so I doubt many people would undergo it just for gender choice purposes.
Embryo Transfer - The doctor and patient will go over the embryo reports and decide how many embryos to transfer to the woman’s uterus. The average in the US is three. More may be transferred under certain circumstances, but only if high order multiples is very unlikely. The transfer itself is a simple procedure; a catheter is inserted through the woman’s cervix into her uterus and the embryos transferred with a small amount of the culture media. Placement is important so this procedure is done under ultrasonic guidance.
Support, monitoring and follow-up - After transfer, the patient will take pregnancy support drugs, like progesterone, which is usually self administered as an intramuscular injection, but suppositories and intravaginal gels are also used. A pregnancy test, called a beta blood HCG test or “beta” for short, is given anywhere from 8-14 days post transfer. Amongst people undergoing IVF, this time period is called the 2-week wait (2WW on message boards) and is considered the worst part of the whole process.
If the first beta is positive (what constitutes a positive depends on the day post transfer and the clinic), a second test will be done 2 days later. In a healthy early pregnancy, this number will approximately double every 48 hours, confirming the positive. Sometimes, the embryos will implant, producing a positive beta, then fail or disappear before the second beta. This is called a chemical pregnancy and is very common.
An ultrasound is usually performed at about 5 weeks post egg retrieval to determine the pregnancy is within normal growth parameters, and to see if multiple gestation sacs are present. Two weeks later, at 7 weeks post retrieval; another ultrasound is performed specifically looking for a heartbeat. If a heartbeat is detected, the chance of miscarriage drops to 2% from 30%, and the patient can be released to her regular obstetrician.
ZIFT and GIFT: These two procedures are not as common as IVF, but still may be indicated depending on the diagnosis. The thinking behind them is that it’s best for things to happen within the body as much as possible.
GIFT stands for gamete intrafallopian transfer. In this procedure, a woman’s ovaries are stimulated with drugs to produce a number of eggs, the eggs are retrieved, mixed with processed sperm, and the resulting mixture placed in the fallopian tubes under laparoscopic guidance. Fertilization then may happen naturally within the tube.
ZIFT stands for zygote intrafallopian transfer. This procedure involves elements from both IVF and GIFT. The ovaries are stimulated and eggs retrieved, then the eggs are fertilized in vitro. The fertilized eggs (zygotes) are then transferred to the fallopian tubes under laparoscopic guidance to divide and grow and travel to the uterus.
[B]The Roller Coaster
In closing, I would like to discuss the physical and emotional aspects of IVF treatment from my personal experience, so you may support a loved one, or prepare yourself.
The drugs mimic the symptoms of menopause, PMS, and pregnancy respectively, while magnifying them in intensity and condensing them into a single month. The side effects can be overwhelming to some women and barely noticed by others.
Egg retrieval is a minor surgery involving recovery from anesthesia and trauma. Do not expect to bounce back immediately.
In almost all phases, there is no place for modesty or sexual privacy. You may be spread eagle in the stirrups with no covering while technicians and nurses walk in and out. Men, you will be given a cup and told to go to "the room" where everyone knows what you are doing and touching the "reading materials" is ill advised. You may be prescribed sex and have it written on a calendar or instruction sheet. You will be asked questions about cervical mucus and bowel habits and sexual positions. If you are a shy, private person, I suggest you find a way to cope with this BEFORE being subjected to it.
You may find yourself resenting each other, or laying blame on your significant other if he or she is the “infertile” one, or blaming yourself and taking it out on your partner. Please keep the lines of communication open, be understanding and forgiving, and try to face this as a team; many couples have broken up over infertility because they couldn’t stand the strain.
In short, please try to empathize with your loved one (and yourselves for that matter) who may be exhausted, bloated, broken out, in pain, experiencing a host of gastrointestinal problems, ashamed, and overly emotional as well as anxiety ridden about the outcome.
[B]Resources
Rhonda Levy (http://www.rhondalevy.com/choosingclinics.htm) will give you her claimed exhaustive research and the names of the top clinics in the US for a consultation fee, but I have no idea how accurate or helpful her information is.
Betabase Info (http://www.betabase.info): a couple undergoing IVF and seeing how women obsess over their beta numbers and doubling times created a self reporting database to show the huge variances
Three day versus blastocyst transfer debate:
Article from Haveababy (http://www.haveababy.com/infert/day3vday5.asp?site=)
Article from INCIID (http://www.inciid.org/asrm/day5or3.html)
Article from Advanced Fertility (http://www.advancedfertility.com/blastocystpregnancyrates.htm)
Empty Arms (http://www.vocalicious.com/empty_arms) A beautiful flash movie about infertility designed by Zuzu at Ovusoft Forums.
Book: In Vitro Fertilization: The A.R.T. of Making Babies (http://www.infertilitybooks.com/titles/in_vitro_fertilization_art_making_babies.html)