Friday, 19 July 2013

Assessment of low and high beta HCG: Unveiling the Secrecy

If you visit any forum or infertility group discussion; you are sure to find questions and worried about HCG levels. The posted inquiries run the gamut from “is my beta too low,” to “do you think my number is high enough to indicate twins?” After my initial beta I was one of the many searching out information on HCG and whether or not my number was good or bad. Looking at other people’s beta levels and doubling times really can help ease some of the worry that goes along with just not knowing what it all means. On that site they only put betas in the chart once a heartbeat has been detected so it can be reassuring to read that there was a successful pregnancy that began with a beta level of 3 at fifteen days past ovulation or that some of the successful pregnancies had slower than average doubling times.

The craziness surrounding beta HCG levels is kind of unique to the world of infertility. People who conceive naturally often don’t even think about their HCG levels unless something goes wrong and the doctor orders the quantitative test. Those who have been through treatment spend their two-week wait counting down the days until beta day. If you are lucky enough to get a positive beta, try counting down the days until the second beta so you can get the more important information of your doubling time or even better (and much more difficult) see if you can hold out and not freak out until your ultrasound at 5-6 weeks. The first ultrasound will tell the tale of your pregnancy much more accurately and if you can do it; you will save yourself much worry and concern.

The hormone human chorionic gonadotropin (better known as HCG) is produced during pregnancy. It is made by cells that form the placenta, which nourishes the egg after it has been fertilized and becomes attached to the uterine wall. Levels can first be detected by a blood test about 11 days after conception and about 12 - 14 days after conception by a urine test. In general the HCG levels will double every 72 hours. The level will reach its peak in the first 8 - 11 weeks of pregnancy and then will decline and level off for the remainder of the pregnancy.

“An HCG level of less than 5mIU/ml is considered negative for pregnancy, and anything above 25mIU/ml is considered positive for pregnancy.”

Each and every patient or couple undergoing IVF, makes a huge emotional, physical and financial investment. The fact that receiving the result of the beta HCG (human chorionic gonadotropin) pregnancy test represents the first decisive hurdle that must be confronted, makes this a very big deal!! The few days after the embryo transfer, waiting for this first outcome report from your fertility clinic is usually anxiety ridden and highly stressful. It is thus imperative that the Fertility Specialist and his/her staff deal delicately with the transfer of this critical information. Dropping the ball at this time would be unconscionable. The physician and staff must make themselves accessible to the patient/couple and communicate the results promptly, professionally and with sensitivity.

A single HCG reading is not enough information for most diagnoses. When there is a question regarding the health of the pregnancy, multiple testing of HCG done a couple of days apart give a more accurate assessment of the situation.
The HCG levels should not be used to date a pregnancy since these numbers can vary so widely.

HCG levels in weeks from LMP (gestational age)*:

      1.       3 weeks                               LMP:      5 - 50 mIU/ml
      2.       4 weeks                               LMP:      5 - 426 mIU/ml
      3.       5 weeks                               LMP:      18 - 7,340 mIU/ml
      4.       6 weeks                               LMP:      1,080 - 56,500 mIU/ml
      5.       7 - 8 weeks                         LMP:      7, 650 - 229,000 mIU/ml
      6.       9 - 12 weeks                       LMP:      25,700 - 288,000 mIU/ml
      7.       13 - 16 weeks                     LMP:      13,300 - 254,000 mIU/ml
      8.       17 - 24 weeks                     LMP:      4,060 - 165,400 mIU/ml
      9.       25 - 40 weeks                     LMP:      3,640 - 117,000 mIU/ml

Non-pregnant females: <5.0 mIU/ml and Postmenopausal females: <9.5 mIU/ml

* These numbers are just a Guideline- every woman’s level of HCG can rise differently. It is not necessarily the level that matters but rather the change in the level.

What can a Low HCG level mean?
A low HCG level can mean any number of things and should be rechecked within 48-72 hours to see how the level is changing. A low HCG level could indicate:

  v  Miscalculation of pregnancy dating
  v  Possible miscarriage or blighted ovum
  v  Ectopic pregnancy

What can a high HCG level mean?
A high level of HCG can also mean a number of things and should be rechecked within 48-72 hours to evaluate changes in the level. A high HCG level can indicate:

  v  Miscalculation of pregnancy dating
  v  Molar pregnancy
  v  Multiple pregnancy
  v  Should my HCG level be checked routinely?

While it can be interesting to see what other people’s beta levels are it is important to remember that the number itself is not the most telling or reliable. HCG is the hormone made by pregnancy that is detected to indicate that a woman is pregnant. In general HCG levels will double every 2-3 days in early pregnancy. 85% of normal pregnancies will double every 72 hours and doubling is often more important that the actual HCG number. There is definitely a large variation in “normal” HCG numbers, and it is advisable to resist the urge to compare to others. That being said, I know from personal experience that it is really hard not to seek out information about the levels and even more difficult to just wait patiently for the ultrasound as recommended.

At least two quantitative beta HCG blood tests are done (2-4 days apart). The reporting of “beta” pregnancy test results is best deferred until after the 2nd blood test results are in. This is because a successful IVF outcome will (in younger women) result at best in 50-55% of cycles (with the notable exceptions of IVF using an egg donor and the transfer of genetically [CGH] tested “competent” embryos).  Thus, it is important to counsel patients in advance of them undergoing beta HCG testing to have rational expectations. It is equally important to inform patients exactly how, when, and from whom they will receive the report of their beta HCG results, because they are about as likely to get “bad news” as they are likely to hear “good news”. Thus I usually advise my patients to “prepare for the worst while hoping for the best” and that in the event of a “negative” result they will have prompt access to me (or a designee) for counseling.

As soon as an embryo begins to implant and its root system begins to invade the uterine lining.  it starts to release the “pregnancy hormone” human chorionic gonadotropin (HCG) into the recipient’s blood stream. About 12 days after egg retrieval, 9 days after a day-3 embryo transfer and 7 days after a blastocyst transfer, the woman should have a quantitative beta HCG blood pregnancy test performed. By that time almost all HCG injected to prepare the developing eggs for egg retrieval should have left the woman’s bloodstream. Thus the detection of >5 IU of HCG per ml of blood tested is an indication that the embryo has attempted/begun to implant. Since with third-party IVF (i.e. Ovum donation, gestational surrogacy, embryo adoption) or frozen embryo transfers, no HCG “trigger shot” is administered, the detection of any amount of HCG in the blood is regarded as significant.

Often times, an initial rise in HCG (between the 1st and 2nd test) will be slow (failure to double every 48 hours). When this happens, a 3rd and sometimes even a 4th HCG test should be done at 2-day intervals. A failure to double on the 3rd and/or 4th test is a poor prognostic sign. It usually indicates a failed or “dysfunctional” implantation but in some cases a progressively slow rising HCG level might point to a tubal (ectopic) pregnancy. Diagnosis requires additional serial blood HCG testing, ultrasound examinations and clinical follow-up to detect any symptoms or signs of an ectopic pregnancy.  

In some cases the 1st beta HCG level starts high and then drops with the 2nd test, only to re-start doubling every 2 days thereafter. This sometimes suggests that there were initially more than one embryo implanting and that one of these subsequently succumbed and one survived to continue a healthy singleton pregnancy. It is customary for the IVF clinic staff to call the patient/couple (and when applicable, notify the referring physician) with the results of the HCG pregnancy test. Often times, the IVF doctor or nurse-coordinator will work through the office of the referring physician to arrange for the all pregnancy tests to be done. If the patient/ couple prefer to make his/her/their own arrangements, the IVF program should provide them with detailed instructions as to how/when and where these tests should be done.

In the event that serial blood quantitative beta HCG pregnancy tests indicate that one or more embryos are likely to be implanting, some IVF physicians advocate daily injections of progesterone or the use of vaginal hormone suppositories for several weeks to support the implanting embryo(s). Others, including several physicians prefer to prescribe HCG injections three times a week for several weeks until the pregnancy can be defined by ultrasound. Some IVF centers do not prescribe any hormones at all, after the transfer.

Patients who undergoing frozen embryo transfer, egg donor, or surrogate cycles and who have blood HCG levels that show the appropriate 2-day doubling; will receive estradiol and progesterone injections and/or vaginally administered hormone suppositories, for 10 weeks following the diagnosis of implantation by blood pregnancy testing. A “clinical pregnancy” is defined as one where there is clear ultrasound evidence of an intrauterine gestation. Such confirmation is usually sought two to three weeks after the first “positive” beta HCG test.

A chemical pregnancy is one where in spite of the beta HCG test being positive it fails to progress to the point of ultrasound confirmation. Chemical pregnancies occur quite frequently following IVF. While they usually result from a chromosomally abnormal embryo trying to implant, they can also be due to the uterine lining (being insufficiently receptive to allow healthy embryo implantation. Clearly, to the IVF patient, the diagnosis of a “chemical pregnancy” represents a severe disappointment. However its occurrence provides clear evidence that at least one embryo reached the advanced preimplantation phase of development went on to “hatch” and attempted to implant.

The chance of miscarriage progressively decreases from the point of diagnosing a viable clinical pregnancy. From this point on, the risk of miscarriage is usually less than 15% in women under 39 years of age and less than 35% in women in their early forties.

Conveying news of a “positive” beta HCG result is easy. Everyone feels elated and vindicated; It is dealing with the unsuccessful case that offers the real challenge. In this regard, nothing is more important than establishing rational expectations from the get-go. In some cases, the patient/couple will crack under the emotional pressure and will require referral for counseling and in some cases psychiatric therapy.

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