The holidays can be especially tough for those struggling with fertility problems.  So much of the season centers around family and children. It can be hard for infertile couples to be around other people’s kids when they are having trouble starting their own family. Here are five simple steps to help make the holiday season a time of anticipation and joy instead of anxiety and sadness.

1. Be proactive. Take charge of your own fertility and regain control of your reproductive life. If you are having trouble conceiving on your own, speak to your physician or to a fertility specialist.  If already in treatment but not yet successful, make a plan for the future. Feeling comfortable with the treatment plan can decrease stress and give you the strength to face the challenges of the season.

2. Keep busy. The less time you have to obsess about why it hasn’t worked yet, the better you will feel.  Spending too much time online might not be a good thing. Get outside and be active.  Increasing exercise often helps fertility patients make better quality eggs.

3. Volunteer. This time of year many organizations need help. A small contribution of your time can help you feel useful and help to brighten someone else’s holiday. Thinking of others will take your mind and energy off of worry about your own unfulfilled dream. Think “Karma” – if you do good things for others, good things will come to you.

4. Don’t forget to take care of yourself. At this time of year, remember that you deserve to be happy even if you are not pregnant yet. Treat yourself to a massage or to something special. Travel with your partner while you can; it gets harder once you have children.

5. Enjoy the family you have. The holidays are supposed to be a happy time focused on the good things in our lives and on those close to us. 

The bottom line: Appreciate the positive. Don’t let people or situations get you upset.  Keep focused on your goal!

Every patient wants to know if the medical treatment they are considering will be successful.  Fertility treatment is an especially costly gamble, both emotionally and financially, so it is not surprising that an informed consumer wants to go where they have the best chance at successful treatment.  Unfortunately it can be difficult to determine who is truly the “best” given competing claims, inflated percentages and manipulated statistics. 

Today’s internet savvy patient needs to sort through exaggerated claims, and try to compare “apples to apples.”  This seemingly simple task is harder than it should be. It is also important to remember that in an individual patient, the outcome of a given IVF cycle is either zero or 100%.

The first issue is defining “success.”  Everyone uses the word, everyone wants it, but what does it really mean? To us it means delivering a healthy baby, generally a singleton.  However, it takes nine months after the treatment to know how the pregnancy will turn out. By that time, patients are no longer under our care and we cannot always obtain accurate outcome data.

For this reason we often use the term “ongoing clinical pregnancy” to represent a gestation likely to result in a baby. If the growth and heart beat are appropriate at 8-9 weeks of gestation, the loss rate falls to about 3%. This is the stage when we usually graduate patients out of our program and refer them for prenatal care. While not as good as the gold-standard of live birth, ongoing clinical pregnancy is accepted by most clinicians in the field as a valid substitute measure of outcome.

Other measures of fertility treatment outcome are less useful. A positive beta hCG pregnancy test is nice, but does not give us enough information, since many cycles that initially result in a BFP will ultimately end in a first trimester miscarriage or biochemical pregnancy.  Even after documenting fetal heart activity at 6-7 weeks, the miscarriage rate is still significant, ranging from 15% in a 30 year old to 40-50% in a 42 year old.

Cycle characteristics such as peak estrogen level, number of follicles, number of eggs, and number of embryos are what we term “secondary outcomes” and are not that useful in predicting outcome, since some patients with only one poor little egg may get a baby, while others with many seeming good quality embryos will not.

The second issue is defining success rate per what? A rate implies a nominator and a denominator. In comparing live birth or on-going clinical pregnancy rates it important to be sure we are using the same denominator. The gold-standard would be outcome per cycle start, which includes all patients who start a cycle. Many centers report data per embryo transfer. Since not all patients who start a cycle will have an embryo transfer, the birth rate will be higher if reported per transfer than per cycle start. When comparing clinics it is important to compare apples to apples.

Since 1992, all fertility clinics are required to submit annual data to the Centers for Disease Control (CDC). The CDC website lists individual clinic and cumulative data for all fertility practices in the country. The cumulative data is more useful than the individual clinic data because the numbers nationwide are so large they can compensate to some degree for variations in individual clinics.  Patients should look critically at programs with individual numbers that are much higher than the national averages.

There are other hidden factors that can influence a clinic’s rates. For example the data reported to the CDC is entered by hand and human error is unavoidable t o some degree no matter how careful we are. On the other end, there is no validation of the data that is entered. While we assume most clinics are honorable, there is really no way to know if the data submitted is true, let alone correct. In addition, some clinics engage in more nefarious practices, such as assigning poor prognosis patients to “experimental” protocols and then do not count them in the data they report. This can lead to numbers that appear to be much better than everyone else seems to be getting.

In fact, because of the lack of quality assurance in the current data reporting system, we at SIRM Las Vegas have chosen to be listed as non-responders until an adequate way of verifying the reported data becomes available. We continue to collect our own data and try to provide IVF outcome statistics for patients in a useful and transparent way.

Various sources have stated that it is not a good idea to take birth control pills before IVF – or before starting controlled ovarian stimulation (COS) in a cycle of IVF.  The reason quoted is that it can suppress the development of ovarian follicles, prolong the stimulation regimen, and negatively impact egg/embryo quality.  This is only half of the story and therefore renders this line of reasoning incorrect. 

It is a fact that if a woman goes directly from Birth Control Pills to ovarian stimulation without overlapping the last several days on the pill with a GnRH agonist (GnRHa) such as Lupron, Nafarelin, or Buserelin, this can negatively affect the stimulation. However, if GnRHa is given for the last 4-6 days on the Pill prior to beginning COS with gonadotropins, this will NOT be the case. Let me explain why:

Toward the end of a natural ovulation cycle, beginning several days prior to menstruation, the corpus luteum (the structure that produces estrogen and progesterone after ovulation) starts to fail.  At the same time, blood levels of follicle stimulating hormone (FSH) begin to rise, which triggers the final process of egg recruitment and antral follicle development.  Absent this FSH triggering, egg and follicle preparation are more likely to be compromised.

The mechanism of action of the birth control pill (BCP) is through suppression of FSH release by the pituitary gland, blocking ovulation and preventing formation of the corpus luteum.

The problem occurs when a woman is on BCP and immediately begins ovarian stimulation upon menstruation following discontinuation of the pill.  In this case, she would be initiating the stimulation without allowing the process of egg recruitment and antral follicle development to be completed.  As a result, follicular response to the stimulation will usually be delayed and blunted. In the process, follicle and egg development are often compromised, and the length of the ovarian stimulation cycle is prolonged significantly.  This helps to explain why there is a perception that the birth control pill can be detrimental to IVF outcome.  In reality, it is only the case when ovarian stimulation is initiated immediately following discontinuation of the pill. 

In my opinion, it is not only acceptable, but even desirable to take the birth control pill for at least one cycle prior to starting ovarian stimulation for in vitro fertilization.  This allows the patient to better plan and time her IVF treatment.   

Additionally, since the birth control pill also suppresses LH, it can be very helpful in older women, in those with diminished ovarian reserve, and in those with Polycystic Ovarian Syndrome (PCOS).  In the latter, high LH levels can negatively impact egg/embryo quality).
The bottom line is that the use of a birth control pill to prepare for an IVF cycle should always be overlapped with a GnRHa for several days before ovarian stimulation begins. If this is done, the pill will NOT suppress or compromise response to COH.

The good news is that normal pregnancies generally do not need any help.

Everyone tends to think of  pregnancy like getting a new kitten.  You are responsible for it, and it is your fault if something happens to it.  In reality, a pregnancy is much more like a parasite that has invaded the woman’s body and taken over her brain. They are not so much cute and cuddly at this point as ruthless, tenacious and hardy. A normal embryo can take care of itself in most any uterus.

Implantation ends with the placenta invading the maternal blood supply.  It then secretes hormones that alter the mother’s metabolism. A normal pregnancy will suck the oxygen, glucose and iron out of the mother’s blood to meet its needs. The mother often gets sick before the baby does.  We have seen normal pregnancies do well despite thin uterine lining or a fibroid uterus.

No news is generally good news.  Also, be careful what you wish for.  Not every normal pregnancy has symptoms of nausea and vomiting.  Those that do have them don’t want them and cannot wait for them to go away.

In contrast, a genetically abnormal pregnancy cannot make a normal baby.

The genetics of the egg are determined when that particular egg gets ovulated. Once an egg is in the laboratory the egg quality is determined.  Many genetically abnormal embryos can fertilize and grow.  It is reported that 70% of “good appearing” embryos on day 3 are actually genetically abnormal.  Furthermore, 40% of good appearing blastocysts are abnormal.

With the advent of PGD we can compare the genetics with embryo development. What we find is that most genetically normal embryos tend to develop into blastocysts. We also see that the majority of embryos that arrest, either on day 3 or day 5, are genetically abnormal.

If a pregnancy is genetically abnormal it will probably fail in the first 8 weeks.

Most first trimester loss is genetic, related to a bad egg rather than the mother’s ability to carry. In some cases, such as a small sub chorionic hemorrhage, fluids and bed rest can help the placenta reattach.  If you have clotting issues a low dose anticoagulant like Lovenox may help.  If you are hypothyroid and are taking thyroid hormone replacement, it is often necessary to increase your medication dose once you are pregnant. If you have immunologic issues, Intralipid infusions may be added.

Adding progesterone will not save a genetically abnormal pregnancy. A low progesterone level indicates the pregnancy is not doing well.  It is low because it is failing, not the other way around.

In fact, when a genetically abnormal pregnancy fails it is often a blessing in disguise. While always sad, if it must fail, we prefer it to happen as early as possible.  This includes not transferring embryos if they arrest. 

In the near future, I anticipate all embryos will have genetic testing prior to transfer. It will never give us a 100% delivery rate, but it will help us to identify genetically abnormal embryos that will either result in babies with chromosomal disorders, or a failed pregnancy/miscarriage.  These embryos are essentially doomed to fail from the start and should never have been transferred.

 The short answer to this question is – not necessarily.  Bleeding during pregnancy is not “normal,” however it is pretty common. About 40% of all pregnant women will experience bleeding heavier than a period. Only about half of those who bleed this heavily will ultimately miscarry. Fifty percent of women who bleed heavier than a period will NOT miscarry. 

In the IVF setting, the most common cause of bleeding we see is caused from the vaginal suppositories irritating the outside of the cervix. This will not affect a pregnancy at all.

Even if the bleeding is coming from the uterus, all is not lost. The placenta is stuck to the wall of the uterus like a suction cup or a stamp on a letter. Underneath, the pregnancy is sitting in a pool of maternal blood. If one corner of the stamp comes loose, then some of that blood will leak out. It does not mean the whole thing will fall off. We call a loose corner a subchorionic hemorrhage, which is a collection of blood and clot behind the placenta. If the bleed is small it will usually resolve on its own with bed rest and fluids. However, even a large bleed does not ensure the pregnancy will fail. Many women bleed throughout pregnancy, some hospitalized and receiving blood transfusions.  Even in these extreme cases we usually end up delivering a healthy baby.

When the Beta hCG level rises slower than expected there can be several explanations. Most commonly it indicates a pregnancy that may be failing.  In this case, the level may peak and then fall back to zero.  We call this a “biochemical”  pregnancy, meaning the only way we knew you were pregnant was from the biochemical test for the hormone level.  While it is always sad to lose a pregnancy, most biochemical pregnancies are genetically abnormal and would never have made a healthy baby.

Another more worrisome possibility is that the pregnancy some how got outside of the uterus and is growing in the fallopian tube. This is called an ectopic pregnancy.  Many people do not realize that IVF increases the risk of ectopic pregnancy over natural conception.  One reason we follow the BhCG level so closely, testing early and making sure the rise is appropriate, is to ensure it is not an ectopic pregnancy.  Fortunately the risk of ectopic pregnancy after IVF is still small.  If we identify one, it is usually also easily treatable with medication.  Surgery for ectopic pregnancy following IVF is usually not necessary.

A slowly rising BhCG does not always mean you will lose the pregnancy. In some cases, the pregnancy may have started as twins and one failed, but the other survived.  In this case, we might see a slower than normal rise or even a slight dip, but then the level recovers and starts to rise normally.

Testing at the same lab and in multiples of two days apart allows us to more easily interpret the levels and eliminates the possibility of variation between labs. Now that BhCG testing is standardized, this has become less of an issue.

Pregnancy is traditionally dated by the start of your last period. However, with IVF, we know the conception day. This is the day of egg retrieval. You are already two weeks pregnant at this point. You will be about 4 weeks pregnant when we can detect the hormone levels in your blood.

One the Beta hCG level gets into the 5,000-10,000 range it may not completely double any more. Sometimes it does not even rise 66% any more. This is not a reason to panic. In these cases the ultrasound findings are usually still good. The hormone levels are a good way to monitor the pregnancy in the early weeks, but after about 5 weeks, ultrasound is more helpful in determining viability.

A heart beat of 120 bpm at 7 weeks is a good sign. Appropriate growth in the next two weeks with a fetal heart beat around 170 bpm and possibly fetal movement are good signs of a healthy pregnancy. If things look good at 8+ weeks, then the chance of miscarriage becomes very small -  about 3%. If you make it to this stage, we can say you are pretty much “out of the woods.”

The culmination of an IVF treatment cycle and the real “moment of truth” is  the post-IVF pregnancy test - known as the “beta hCG” or simply the ”beta.”   A woman is considered pregnant if an embryo has implanted into her uterine lining.  This embryo implantation involves the embryo  ”invading” the uterine blood supply. We can identify that this has occurred by detecting the hormone hCG (human chorionic gonadotropin) in the mother’s bloodstream. This hormone has two parts – alpha and beta. We measure the beta portion of the hCG molecule (BhCG).  The presence of this hormone in a woman’s blood indicates she is pregnant.

Some other tissues in the body, like skin, as well as certain tumors, can also make hCG. This is why women sometimes have a level above zero, but under 2.0.  We call a woman pregnant if the level is above two and, more importantly, is rising appropriately.  The actual number is not that important because there is a huge variation of normal levels. What is important is that the hCG level doubles every 2 days.  The rule is actually a 66% rise in 48 hours, though in the early stages, we do think a complete doubling is important.

Timing of the beta hCG test is also important. We usually test at 11 and 13 days after ovulation. At this stage we can detect a level above 2 and we can be confident the value will not be affected by the hCG shot used to trigger ovulation.

Blood levels are more trust-worthy than urine tests, which can usually only detect a hormone level of 50 or more. We test early, so even the most sensitive urine tests (that can detect a level of 20) will often be negative when we test. The reason we test twice is to evaluate the rise.

In part I of this two part series, I discussed the scope of Recurrent Pregnancy Loss  (RPL) and three of its known etiologies.  These included genetic, immunologic and hormonal causes, and their management options. In this part, we will discuss the remaining two causes and management options. 

Infectious causes have been implicated in RPL.  Specifically, bacteria such as Ureaplasma and Mycoplasma that can colonize in the uterine cavity have been implicated in RPL.  These conditions can be detected by simply culturing the cervix.  If these bacteria are isolated, simple antibiotic treatment can be used to eradicate them.

Anatomic disorders can be congenital or acquired.  Anatomic disorders can typically be diagnosed with the use of ultrasound or occasionally an MRI.  Sometimes surgery is necessary for diagnostic as well as therapeutic measures.  Congenital anatomic disorders occur during embryologic development when the uterus is undergoing development.  These disorders can include such defects as:

• A uterine cavity divided into 2 smaller compartments, known as a septum
• An incompletely fused uterus that has a heart shape, known as a bicornuate uterus
• A double uterus known as didelphic
• A halved uterus known as unicornuate.  The mechanism by which miscarriage occurs in these disorders can be secondary to aberrant blood flow and/or poor structural integrity of the implantation site.  Congenital disorders can sometimes be surgically corrected; however, not all of them require treatment. 

Acquired anatomic defects include benign muscular tumors, known as uterine fibroids, or benign outgrowths of the uterine lining known as polyps. Both of these conditions can interfere with implantation, and can be surgically repaired, often through minimally invasive surgeries. 

Your doctor can help you sort through the possible causes and treatments of RPL.  Even after multiple miscarriages, there is high chance that a successful pregnancy can be achieved.

It has been suggested that the upper limit of normal for Thyroid Stimulating Hormone (TSH) in infertile women who are trying to conceive should be 2.5 mIU/L instead of 4.5 mIU/L as is used by most laboratories.  A TSH level greater than 2.5 mIU/L, in the setting of a normal serum free thyroxine (T4) concentration, is associated with a disorder known as subclinical hypothyroidism.  People with subclinical hypothyroidism tend to be asymptomatic, but it has been associated with adverse pregnancy outcomes in infertile women.

Infertile women who have subclinical disease are at increased risk for miscarriage, preterm delivery, low birth weight, as well as neuropsychological and cognitive impairment of the child.  In light of the adverse outcomes associated with subclinical hypothyroidism, thyroxine replacement is recommended in those who are infertile and wish to become pregnant.  The goal of therapy is to reduce the patient’s serum TSH concentration to 1-2.5 mIU/L.  I usually give the lowest dose of thyroid hormone to normalize the serum TSH concentration and to avoid overreplacement.

With a positive pregnancy test, it is also important to remember to increase the thyroxine dose by 30% because thyroid requirements increase during pregnancy.  Serum TSH levels should be measured 4 to 6 weeks after conception and after any change in the dose of thyroxine, and at least once each trimester.  Adequate replacement of thyroid hormone in infertile women with subclinical disease may help to obviate some of the adverse outcomes associated with this disease.