PFC is proud to announce that all 5 Pacific Fertility Center Partner physicians have been named Top Reproductive Endocrinologits on the U.S. News Top Doctors list.  Drs. Philip Chenette, Carolyn Givens, Carl Herbert, Isabelle Ryan, and Eldon Schriock were selected as top doctors based on a peer nomination process.

Congratulations to each of them on this incredible honor!

Miscarriage, which is the loss of a pregnancy before 20 weeks of gestation, is a common outcome of human pregnancy. Spontaneous pregnancy loss (a “pre-clinical” miscarriage) can happen very early, sometimes before a woman even knows she is pregnant or can occur later, with heavy bleeding or cramping or loss of recognizable fetal tissues. Sometimes a lost pregnancy is discovered by ultrasound exam when there is no viable fetus. When including early pre-clinical and clinical pregnancy losses, approximately 31% of all pregnancies are lost prior to birth1. The vast majority of pregnancy losses are sporadic, unpredictable and can occur for a variety of reasons. About 1% of couples experience recurrent pregnancy loss, which is the loss of 3 or more consecutive pregnancies. Recurrent pregnancy loss can be due to more than one problem, but it is less likely

So what is the reason behind the high percentage of human pregnancy loss? On an evolutionary, teleological level, human pregnancy loss rates, which are high compared to other species on the planet, may be due to the fact that raising a human infant/child to the level of independence is a very labor-intensive job for human parents. Perhaps miscarriage is one of the means, albeit a sad one, of not having too many successful pregnancies in a row and for a mother to recover fully from one pregnancy before having the next. This theory is, of course, speculative on my part and I will never be able to prove it. However, it seems to me there must be some reason why humans are built to abort almost 1 out of every 3 conceptions.

Speculative reasons aside, what is the underlying mechanism for miscarriages? There are two major areas involved: fetal reasons and maternal reasons. The evidence suggests that, in the overwhelming majority of cases, there is something wrong with the fetus.

Embryo and fetal abnormalities can include abnormalities in chromosome number – i.e. having an extra or a missing chromosome, also known as aneuploidy – or can be a sporadic, non-chromosomal abnormality that makes further development incompatible with life, for example, a major heart defect. Aneuploidy (having an incorrect number of chromosomes) is exceedingly common in human pregnancies, especially as a woman ages. Aneuploidy accounts for over half of all sporadic, spontaneous pregnancy losses2. It is also a common cause of failure of early embryos to implant in the uterus. The maternal age-related incidence of aneuploidy of human embryos can be seen in this table of data from Gene Security Network, a laboratory that performs genetic analysis on human embryos using DNA micro-array technology:

This data shows that even in women less than 30 years of age, almost 60% of embryos at 5 days of life are abnormal. However, aneuploidy does not explain the entire picture with regards to implantation success or miscarriage. One recent study found that that using newer DNA analysis techniques, some aborted fetuses showed gene abnormalities that would not be identified using the common genetic methods currently used to evaluate fetal DNA3. These studies suggest that there are sub-chromosomal level abnormalities that also contribute to human fetal wastage. One interesting area of research has involved performance of embryoscopy, (using a lighted scope to visualize an intact fetus) prior to performing a dilation and evacuation procedure (D&C, D&E), a procedure which may render the tissues unrecognizable. These video images have shown us that a substantial number of non-viable human fetuses have recognizable abnormalities, even recognizable in the first trimester, and that not all of these anatomic anomalies are associated with chromosome abnormalities 4-5,

Implantation and the successful early-stage development of an embryo is an exceedingly complex process. On the maternal side, there are a large number of growth factors and other molecules that must be expressed on cells as well as complex anatomic and physiologic processes that must occur for the process to result in a successful live birth6. There is little doubt that some uterine abnormalities can cause a normal embryo to fail to survive. These include congenital abnormalities such as a uterine septum (abnormal shape of the uterine cavity) or acquired abnormalities such as uterine fibroids that distort the endometrial cavity. The majority of these abnormalities can be surgically repaired with good results. Other identified maternal causes of fetal loss are rare but include an auto-immune abnormality, anti-phospholipid antibody syndrome, which is mainly associated with second-trimester fetal loss and poor obstetric outcomes. Endocrine abnormalities such as sub-clinical or clinical hypothyroidism (low thyroid hormone levels with or without symptoms) can cause an increase in fetal loss. There is some limited data suggesting women with thrombophilias (tendency for increased blood clotting) may have a higher risk of miscarriage. More difficult to study and substantiate are possible associations between abnormalities in progesterone levels, infection, alcohol and caffeine use.

On the paternal side, there is a growing body of evidence that increasing paternal age may lead to increasing pregnancy losses in their partners7. This effect has been noted in men older than 50 years of age.

In approximately 40% of all pregnancy losses, there is no identifiable cause. This lack of causation may lead to frustration, especially if a couple experiences two or more miscarriages. It is important to realize that miscarriages are common, even in couples with no fertility problems. Miscarriage appears to be a natural phenomenon built into our evolution and in most cases, an occurrence we are not likely to change the odds of happening, unless couples consciously try to have children at a younger age. It is also important to realize that the risks of experiencing a miscarriage do not increase until three or more miscarriages occur. That means, in a woman with one or two miscarriages, her odds of having a second or third miscarriage are the same as for a woman her age that have never had a miscarriage. Only after the third consecutive miscarriage do the odds of having another increase over the age-related background rates.

References:
1.  Incidence of Early Loss of Pregnancy, Wilcox, AJ, et al. NEJM Jul 28, 1988, (319) 189-194.
2.  Cytogenetic analyses of culture failures by comparative genomic hybridization (CGH) – re-evaluation of chromosome aberration rates in early spontaneous abortions. Fritz B et al, Eur J Hum Genet 2001, 9; 539.
3.  Identification of Copy Number Variants in Miscarriages from Couples with Idiopathic Recurrent Pregnancy Loss. Rajcan-Separovic E, et al. Hum Reprod. 2010 Nov;25(11):2913-22. Epub 2010 Sep 16.
4.  Transcervical embryoscopy: images of first trimester missed abortion. Abdala LT et al, J Minim Invasive Gynecol Jan-Feb 2010 17(1):12-13.
5.  Abnormal embryonic development diagnosed embryoscopically in early intrauterine deaths after in vitro fertilization: a preliminary report of 23 cases. Fertil Steril Nov 2004 82(5): 1337-42.
6.  Implantation and the Survival of Early Pregnancy, Norwitz ER et al. NEJM Nov 8, 2001, 345 (19) 1400-8.
7.  The effect of paternal age on assisted reproductive outcome. Dain, L, et al. Fertil Steril Jan 2011, 95(1) 1-8.

Among the most common questions we get as fertility physicians from patients trying to conceive a pregnancy are: how much alcohol is safe to consume and when? Should I stop having any caffeine altogether? How much exercise is safe while trying to get pregnant?

Because comprehensive, high quality studies to address these questions really don’t exist, we try to come up with reasonable advice based on the best data we have as well as data from studies on already pregnant patients, plus just medical common sense. That said, even amongst the six PFC physicians, we vary, albeit only slightly, in the individual advice we give our patients. In this article, I have tried to come up with a consensus opinion based on a poll of the advice all of us give to our own patients.

With regards to alcohol, we are fairly liberal in allowing small amounts of alcohol consumption while trying to conceive. According to Dr. Schriock, “My advice is, if they are trying to get pregnant, to cut back on the alcohol consumption, but if you have a party and you want to have a couple glasses of wine, that’s fine. Less is probably better, but once we do the (embryo) transfer, they shouldn’t drink at all.” Dr. Herbert’s advice is: “Then with alcohol, after embryo transfer or once you are pregnant, there is always a concern with fetal alcohol syndrome. But a glass of wine or cup of caffeine with a full stomach is not a problem.” There was just a recent article suggesting that women who drink more than two or three drinks per week have lower pregnancy rates. Generally I tell people that when they get their period, they can have a glass of wine or beer. But once they have ovulated and are in the luteal phase and they could be pregnant, try and avoid any alcohol at all. Certainly avoid any binge drinking which is very detrimental. Alcohol is also very dehydrating, which is not conducive to conception.

So what about caffeine? Again, the data in regards to caffeine consumption and fertility is very limited. Studies in women who are pregnant have suggested that heavy caffeine consumers (equivalent to 5-6 coffee servings per day) have been found to have higher rates of miscarriage. Dr. Ryan’s advice is “…one to two cups per day, max, even after (embryo) transfer.” Dr. Herbert says: “More than 4-6 cups of coffee a day has a higher risk of miscarriages associated with it, although its direct effect with fertility is unknown. They can drink decaf coffee, which is better, but if they are going to drink caffeinated coffee in the morning, they should have food in their stomach.” My advice is that caffeine is a drug that causes vasoconstriction (narrowing of blood vessels). It’s not a drug you want to expose your baby to when pregnant. Since it is sometimes difficult to stop drinking coffee cold turkey, why not try to wean oneself off of it while trying to conceive? Decaf is fine.

And exercise? How much is too much? What about moderate exercise? Dr. Schriock says “For exercise, there are two studies that I quote. The first specifically looked at IVF patients, and they divided exercise into two categories: high aerobic, example in this group is running and intense cycling, and low aerobic, the example in the low group is walking and yoga. Then they asked patients how long they had been doing that activity. They drew a line at ten years. If you started running five years ago, then it seemed to lower your chances of getting pregnant. However, if you had been running for ten years of more, then it didn’t seem to make any difference. The interpretation of that is that it takes ten years for your body to get used to an activity. But the low intensity group, it didn’t seem to make any difference if you had done the exercises once, twice, five years, or ten years. Low exercise, it doesn’t matter, but high intensity exercise, should be doing it for ten or more years.

The second study I quote is not for how long they have been doing it, but how much they were doing. If they have more than four hours of aerobic activity per week, it seemed to lower pregnancy rates. Then I discuss what would you like to do? And I finally say that this is probably a balance between exercise and stress. Because if you are using exercise as a stress reducer and you take it away, all of the sudden your body gets stressed out. Then I leave the door open to be individualized.”

Dr. Chenette’s advice is that “as far as exercise, I tell them not to do any lifting over 40 pounds. On the day of transfer, they can not do any exercising, but then after that, they can resume their normal exercise regime. However, I tell them to refrain from any exercise that involves jumping. I recommend swimming and Pilates as a source of exercise. I also do not suggest any exercise that will result in weight loss because that means that they are not getting enough calories.”

Dr Ryan’s advice? “For exercise, I say in moderation. No more than four times a week for a max of one hour to 1 ½ hours. Then, in treatment, it needs to be low impact and no hot exercises like Bikram yoga after embryo transfer.” And Dr. Herbert says, “In regards to exercise, I suggest that they do not do any training for an excessive event, like a marathon. Exercise should be reasonable. It depends on their weight and the amount of time that they exercise. It is good to continue to exercise, but in moderation.”

I think the bottom line on exercise is moderation, generally no more than 4 hours of aerobic exercise per week and no exercise with weight loss as a goal. Yoga, Pilates and non-aerobic strengthening exercise is fine but again, more moderation immediately after an embryo transfer.