The following recent query requested my opinion regarding the safety of metformin during the periconceptual period and throughout pregnancy. Although there are not many large or comprehensive studies addressing these concerns, the bulk of the data available to us is encouraging…
Quick opinion if you don’t mind. As you may recall, I miscarried on 9/12. I have since seen my PCP for a regular check-up. He prescribed me Metformin….he believes based on my history, weight, blood work and family history, my body may have issues with the breakdown of sugars (i.e., type 2 diabetes but I’m not diagnosed with that). He said that it also may have some positive side effects for me including weight loss and assistance in helping me to conceive (although that doesn’t appear to be a problem since I WAS able to get pregnant even though I miscarried). He says it is completely safe.
Read more »
This post, Is It Safe To Use Metformin During Conception and Pregnancy?, was originally published on
Healthine.com by Kenneth Trofatter, M.D., Ph.D..
Patient question about “Amniocentesis is Not Without Risk”:
I am 29 years old and am 21 weeks along. I just had an ultrasound a couple of days ago and was told that the nasal bone is not showing up which puts me at higher risk for a baby with Down Syndrome. I have yet to have someone tell me how much of an increased risk. I did not have the 1st trimester screenings as I’ve always said that it wouldn’t make any difference but now that it’s staring me in the face I am seriously considering an amniocentesis. I just wonder if I can go through the next 19 weeks wondering. Can you tell me what my risk is for a Down Syndrome baby? Thank you.
Previously we published a post that discussed the role of assessment of the fetal nasal bone in first trimester screening for fetal chromosomal abnormalities and, in particular, screening for Down syndrome (trisomy 21). Confirmed absence of the fetal nasal bone in first trimester has been correlated with a detection rate for Down syndrome in the range of 70% (with false positive rates dependent on maternal ethnicity – 2.2% in causcasians; 5% in Asians; and 9% in Afro-Carribeans) (Cicero, et al. Ultrasound Obstet Gynecol. 2003;21:15–18; Prefumo, et al., BJOG 2004; 111:109–112). Although determining the presence or absence of the nasal bone can clearly contribute to the risk assessment in first trimester, unfortunately, the technical difficulty of reliably obtaining an image and accurately interpreting the findings have led to more restricted use here in the U.S., even at many major academic centers.
In contrast, in midtrimester genetic screening, often done at 18-20 weeks, the finding of an absent nasal bone and to a lesser degree a hypoplastic nasal bone, is becoming more widely recognized as a major ‘marker’ for trisomy 21. In midtrimester, complete absence of the fetal nasal bone occurs in about one-third of Down syndrome babies. If a ‘short’ nasal bone (nasal bone hypoplasia), is included in the evaluation, 60% or more fetuses with Down syndrome may be detected, again with false-positive rates depending on ethnicity and the variable cut-off values for defining a “short nasal bone” in different studies (Bromley; et al., J Ultrasound Med 2002; 21:1387–1394; Bunduki; et al., Ultrasound Obstet Gynecol 2003; 21:156–160; Lee, et al., J Ultrasound Med 2003; 22:55–60; Gamez, et al., Ultrasound Obstet Gynecol 2004; 23:152–153).
One small study using 3D ultrasound found an absent nasal bone in 9 of 26 babies with Down syndrome (34.6%) and only 1 of 27 (3.4%) chromosomally normal babies, but this also meant that 9 of the 10 (90%) babies in whom complete absence of the nasal bone was found had Down syndrome (Goncalves, et al., J Ultrasound Med 2004;23:1619-27). In a recent study of 4373 babies evaluated in midtrimester, complete absence of the nasal bone was found in about 30% of Down syndrome and only 1% of chromosomally normal fetuses . (Odibo; et al., Am J Obstet Gynecol 2008;199:281.e1-281.e5). Nasal bone hypoplasia, defined in this study as <0.75 MoM, identified 47% of Down syndrome pregnancies and occurred in 6% of normal pregnancies.
So, to our reader, I cannot give a precise estimate of increased risk based on the ultrasound findings you report. However, if the ultrasound was performed by an experienced examiner and adequate images were obtained for evaluation, the complete absence of a fetal nasal bone at 21 weeks, even as an isolated finding, is disconcerting. The risk for Down syndrome could be as high as 90% and the false positive rate 5% or less. And, if you really need to know whether or not your baby is affected, an amniocentesis would be the best way to get that information. Best wishes and please let us know what you find out.
This post, Absence Of Fetal Nasal Bone Is A Marker For Down Syndrome, was originally published on
Healthine.com by Kenneth Trofatter, M.D., Ph.D..
Probably one of the most popular series I have written over the past few years is the one on recurrent early pregnancy loss. There is not a week that goes by that I still don’t get inquiries related to that subject, most accompanied by the pain, frustration, sense of loss, and feelings of hopelessness for future fertility. There are several points I always remind readers and patients about whenever I have the opportunity to discuss their concerns: 1) In most cases, the tincture of time alone offers the answer to their prayers; 2) If specific reasons for their losses are found or suspected, these can often be addressed medically and/or surgically; 3) If specific reasons cannot be identified, there are reasonable approaches to ‘empiric therapy’; and, 4) If these approaches fail, the science of assisted reproductive technology (ART) has advanced to the point that it can often overcome most obstacles that stand in the way of fertility.
The other points I always mention in response to the questions of “Why did this happen to me?”, “What did I do wrong to cause this?”, “What can I do to assure that it never happens to me again?, particularly to couples who have had their first or second miscarriage, or a sporadic miscarriage after successful pregnancies, are the following: 1) Miscarriages occur in 15-20% of all conceptions; 2) The MOST COMMON cause of early pregnancy losses are chromosomal abnormalities that occur by chance (except in the case of parental chromosomal rearrangements) and are not under any controllable influences; 3) It is unlikely that anything was “done” to cause the loss, although if there are such potential factors identified, the loss may provide an incentive to modify lifestyle prior to another pregnancy attempt to minimize their risks.
Recently, I received the query below from a woman who has had early pregnancy losses related to documented chromosomal abnormalities. Despite the other problems that have been identified which might contribute to reduced fertility in her case, these probably had no influence on her babies’ chromosomal abnormalities. But, they do give us the opportunity to briefly discuss the well-known observations that certain seemingly “unusual” chromosomal abnormalities (“unusual” in that they rarely or never result in a live born baby) actually contribute to a relatively high percentage of early pregnancy losses. Read more »
This post, Genetic Causes Of Early Pregnancy Loss, was originally published on
Healthine.com by Kenneth Trofatter, M.D., Ph.D..
I received the two comments below from readers and use this opportunity of their tragic experiences to revisit a concern that I raised about two years ago regarding methotrexate therapy for the presumptive diagnosis of ectopic pregnancy….
Melissa O. said…
I was told I had an ectopic pregnancy and was advised I was in need of a Methotrexate shot. I got it. One week later my hormone level was continuing to rise. Low and behold 4 days later my ultrasound showed I was carrying twins. The Dr.’s had presumed ectopic too early. Getting the shot caused me to loose Twin A and to give birth to a very much underweight 28 weeker. This experience has changed my life forever. My son fought to survive…he continues to today now 13 months old. I would hope anyone who is told they have an ectopic pregnancy would be cautious when it comes to this shot. Yes I agree it helps if your life is in danger due to an ectopic pregnancy. Just take time to ensure there is no doubt that’s what it is. My Dr couldn’t see the baby so assumed ectopic, however carrying twins like I was you’re not able to see as early as a single pregnancy. My son is paying everyday because of my mistake and doing as one Dr. said make sure you have more than one confirmation, it could cost you a perfectly healthy baby in the end.
Fri Jun 19, 05:45:00 PM 2009
Hi can someone help me? My husband and I were trying for a baby and I fell pregnant (good news). I started having a few brown spotting and slight cramping which I was advised by my GP to go to the hospital for a scan. Whilst there I had many tests and the doctors thought it might be ectopic and said he was going to keep me in for a few days to monitor my blood levels. I had a scan but being only five weeks it was hard to say. I was referred to another doctor on the ward and he told me it was ectopic. I trusted his knowledge and he said he needed to give me methotrexate now as it was Friday so the pharmacy would be shut. I was shocked but agreed of course. 3 days later I was told the baby is still alive and is in my womb. My blood levels increased after 3 days and then decreased from 7000 to 6000 on the 7 days. How long will it take to lose my baby as it’s hard to know its alive?
Fri Jul 03, 11:15:00 AM 2009
Ever since methotrexate became popular for treating ectopic pregnancies, I have seen the unfortunate scenario reported by our readers above played out time and time again. Methotrexate (MTX) is an analog of folic acid. It binds tightly to an enzyme called dihydrofolate reductase and when it does so, interferes with the production of tetrahydrofolates. In the end, this interferes with the normal production and repair of DNA by limiting the production of a key nucleotide, thymidine. Other metabolic effects are also known, but the take home message is that MTX can result in lethal damage to cells that are replicating, particularly those that are replicating rapidly, like certain cancer cells.
Because of its documented efficacy in the treatment of malignant trophoblastic cells (choriocarcinoma), MTX has been employed in recent years as an alternative to surgical therapy in selected cases of ectopic pregnancy (Lipscomb, et al. NEJM 2000;343:1325-29). Ectopic pregnancies, by definition, implant ‘outside the uterus’ with more than 95% occurring in the fallopian tubes and about 2.5% in the cornua of the uterus (where the fallopian tubes enter the uterus). For that reason, they are frequently referred to as ‘tubal pregnancies,’ although they can also occur in the cervix, ovary and intra-abdominally. The fallopian tubes cannot restrict the growth of invasive placental tissues, as can the endometrium, and they certainly cannot accommodate a growing embryo beyond a certain point before they rupture and hemorrhage. Indeed, ectopic pregnancies can be quite deadly if not treated appropriately. They are still a major cause of maternal mortality, accounting for 10-15% of all maternal deaths, and they are the leading cause of death in pregnant women in the first trimester. A ruptured ectopic pregnancy is a true medical emergency.
Because of the rising incidence of ectopic pregnancy, the risk (maternal and medical-legal) of not identifying and treating an ectopic pregnancy in a timely fashion, and the widespread acceptance and success of MTX therapy as an alternative to surgical management of an ectopic pregnancy if caught early enough, there has been a coincident increase in the inadvertent use of MTX in unrecognized early intrauterine pregnancies. The usual scenario is one in which the pregnancy is not quite as far along as anticipated and the patient happens to present with complaints of abdominal pain or some spotting and no clear intrauterine pregnancy is identified by ultrasound. The ‘absence’ of an intrauterine pregnancy can be misdiagnosed because the pregnancy really is too early, but in at least one of the scenarios above was more likely the result of the inexperience of the individual(s) performing the ultrasound study.
This situation can be especially confusing if the pregnancy hormone levels (hCG) appear to be low for the expected gestational age based on last menstrual period (as is often seen in women who ovulate later, and hence conceive later, in their cycles) or if a woman has a tender adnexal mass because a hemorrhagic corpus luteum (intraovarian bleeding at the site from which the egg was ‘hatched’) or torsion of an adnexal mass (rare this early in pregnancy) which might be very difficult to differentiate from an ectopic pregnancy.
Since MTX is a category X drug, known to be teratogenic in humans, it is important to ascertain the presence of an ectopic pregnancy rather than simply to use it empirically. Unfortunately, its inadvertent use with an intrauterine pregnancy is most likely to occur during the time of neural tube and very early cardiac development, both of which rely on folate-dependent pathways. Various algorithms are in place that employ ultrasound imaging, quantitative hCG levels, and progesterone levels to differentiate abnormal from potentially normal pregnancies and these protocols can be useful in minimizing the chance of the inadvertent use of MTX and also in directing its use when appropriate for the management of an ectopic pregnancy. Perhaps the greatest risk of ectopic pregnancy is not suspecting that one could be present. Patients who are adequately counseled and followed closely are much less likely to end up in emergency situations.
To our readers above, I am SO SORRY for both of you. This is a failing of the medical system and is a growing concern of mine due to the ready accessibility and simplicity of use of methotrexate (and also another drug, misoprostol, that is used in the ‘medical evacuation’ of the uterus when an inevitable miscarriage is suspected).
My feeling is that it should never be used in an asymptomatic or minimally symptomatic patient until either an ectopic pregnancy is seen, no intrauterine pregnancy is documented (by a competent sonographer) at hCG levels where an intrauterine pregnancy should readily be visible, the patient has significant ‘risk factors’ for an ectopic pregnancy (e.g., previous ectopic, known history of pelvic inflammatory disease or tubal reconstructive surgery) or when there are well-documented abnormalities in the rise of hCG that are highly suggestive of an ectopic pregnancy. My heart goes out to both of you.
This post, Accidental Abortion: Use Of Methotrexate For Misdiagnosed Ectopic Pregnancies, was originally published on
Healthine.com by Kenneth Trofatter, M.D., Ph.D..