Midtrimester Loss: Preterm Labor vs. Cervical Incompetence

Below is a sequence of comments between a reader and me related to the unending difficulties we encounter sorting out the cause of midtrimester pregnancy losses: Is it preterm labor, cervical incompetence, uterine infection, fetal chromosomal abnormality (or some other problem) or a combination of more than one factor? When I trained, I was taught that “if the patient is having contractions, it is preterm labor and not cervical incompetence and a cervical cerclage (stitch around the cervix) was NOT indicated” and many physicians still believe that. But over the years, I have learned that things are not always that simple!

Thanks to the many desperate patients I have had with advanced cervical change in midtrimester (generally, at 24 weeks or less), no evidence of overt infection, but some uterine contractions, who begged me to “do something because we have nothing to lose by trying at this point”, I quickly learned that many of these patients could have their pregnancies salvaged by using broad-spectrum antibiotics, a ‘rescue’ cervical cerclage, and suppressing the uterine contractions. In many (actually, most in my experience) of the cases, the pregnancies carried until there was a good outcome for both baby and mother. The only thing I asked these patients to agree with me on up front was that I would have to end the pregnancy, regardless of gestational age, if there was evidence of intrauterine infection. At that point, the mother’s life is at risk and there is no further benefit to the baby to remain in the uterus.

The series of comments below help you to understand the physician’s thought processes and, to some extent, the patient’s misconceptions, that occur around the always traumatic experience of losing babies in midtrimester. (I apologize to the reader because I have edited some of her comments).

• At Wed Feb 06, 06:57:00 AM 2008, Anonymous said…

Dear Dr T,
After my last miscarriage, my doctor evaluated me for the possibility of a thrombophilia problem but found nothing. Me and my partner have also had our chromosomes examined and both of us were normal. The upshot was that no causes for the miscarriages were found. This leaves me with a lot of questions. Why did I have twice very late miscarriages? Currently I am pregnant again, but I am very afraid that it will happen again. I fear that there is something wrong with me which have caused the miscarriages. How likely is this if I already have had a full term delivery? Could my second miscarriage have been caused by the progesterone injections I was given because of my first loss? Would you advise me to take progesterone injections in this pregnancy (my doctor does). Does progesterone have any adverse effects on pregnancies? I would be very grateful if you would like to answer these questions or advise me further on this.
Kind regards

• At Sun Feb 10, 07:02:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…

To Anonymous Feb 6: Answer several questions for me and then I will be in a better position to respond to yours:

1) Did you have the full-term pregnancy and then have the miscarriages?
2) Did you have any complications with the full-term pregnancy or with the delivery?
3) Did you have a vaginal delivery or a cesarean?
4) Have you had any cervical operations such as LEEP or cervical conization done?
5) How "late" were the miscarriages you had?
6) What were the circumstances surrounding those miscarriages, i.e., did the babies die in utero; did you have premature labor; did you break your bag of waters prematurely; did you have any evidence of 'infection'; did you labor or did your doctors put you into labor; did you receive progesterone with either of those losses; and, do you have any medical problems?

There are reasons for ALL of these questions and the answers will help me get a better idea as to what happened with your previous losses. Dr T

• At Wed Feb 13, 05:17:00 AM 2008, Anonymous said…

Here are my answers:

1) Yes, I had a full-term pregnancy first and had the two miscarriages thereafter.

2) The full-term delivery took very, very long (almost 40 hours from the first signs) and eventually I was given medicine to deliver my daughter. I could not have done it by myself probably. I had heavy bleeding afterwards (post-partum hemorrhage) and was very weak for more than two weeks following the delivery.

3) It was a vaginal delivery.

4) I don’t know what these (LEEP and cervical conization) are, but before having my daughter and the miscarriage, I had two abortions (I was too young then). And after the first late miscarriage the doctor cleaned up my uterus (did a D&C) as the pregnancy product did not leave my uterus completely (retained placenta).

5) The first time the baby was 20 weeks and a couple days old, he was born alive and I had premature labor. After this miscarriage the doctor thought (although I didn't have any infections) that the miscarriage might have been caused by a bacteria (slight increase of granulocytes in my blood) or cervical incompetence. However, he was not sure. I also then had a severe allergic reaction to the antibiotic I was given in the hospital in order to prevent any infections. My blood pressure was 80/40 and I was in very bad condition. So maybe this might also have caused the increase of the granulocytes or even the eventual delivery as I did not have a lot of dilation at first, but the situation got worse after I got the antibiotics.

The second time I delivered at 19 weeks; the baby probably had died at 15/16 weeks. I had no labor at all and was given medicine to deliver. Only in this pregnancy I was given progesterone (starting at week 16 because of the first miscarriage and in order to prevent any cervical incompetence. Again this time there were no signs of infections, and to my knowledge I am healthy and do not have medical problems. My age is 35.

In both cases I did not have break of bags/water.

So this leaves me with questions: Why does this happen so late and do I have to live with the knowledge that this kind of thing happens without reasons? And, could the second miscarriage have been caused by the progesterone as the period the baby died was more or less the period I started with the injections? Would you advise me to take these injections also in this pregnancy?

Would you advise me to take extra vitamins, other than folic acid (as I have been pregnant many times in a relatively short period)? Could this circumstance have played a role (short period in between pregnancies) in my losses? I would be grateful for your answers.

• At Fri Feb 22, 07:06:00 PM 2008, Kenneth F. Trofatter, Jr., MD, PhD said…
To Anonymous Feb 13: I do not think the abortions you had when you were younger contributed in any way to your more recent losses. However, I am worried that the first full-term delivery might have. You could have had damage to your cervix from the difficult labor and delivery or from the D&C procedure that had to be done to stop your hemorrhage.

I believe your first loss at 20 weeks, was the result of cervical incompetence and probably a secondary ascending infection. Once the cervix started to change, the contents (baby, membranes, and placenta) are more readily exposed to the bacteria within the vagina. I am not sure you really had an 'allergic reaction’ to the antibiotics. The low blood pressure and being in “very bad condition” is more consistent with 'septic shock’ resulting from a bacterial infection that had gotten into your blood stream from your uterus. I also do not think either the antibiotics or your 'bad reaction' caused you to lose that baby, it may well have just seemed that way because everything was getting worse after the antibiotics were given, but it was probably too late for them to be of any benefit. Significant infections in the womb will usually cause delivery within 48-72 hours regardless of any antibiotics that could be given to you.

Your loss at 15-16 weeks might also be the result of infection, or perhaps the baby had a chromosomal abnormality and that’s why he/she died. It is VERY unlikely the progesterone alone caused you to lose that baby. Indeed, the baby could have died even before you got the first shot based on the timing you have given to us. However, some people believe that progesterone can possibly reduce your body's ability to fight off some infections (although that has NOT yet been proven), so I will not rule out that possibility completely.

Before you get pregnant again, I would recommend that you have a sonohysterogram and perhaps a hysteroscopy done to evaluate the uterine cavity for any abnormalities that could be present (e.g., fibroids, polyps, scar tissue, and endometriosis). Your doctor might also consider treating both you and your husband with a 10-14 day course of an antibiotic such as doxycycline. I would suggest starting a prenatal vitamin and extra folic acid a month or two before you decide to try again and then, when you do get pregnant, personally, I would recommend placement of a cerclage at 13-14 weeks. I also recommend that before that is done (at 11-12 weeks), you have first trimester screening for aneuploidy (fetal chromosomal abnormality) performed. This involves only a simple ultrasound of the baby and some blood work on you. Your doctors can explain all of these procedures and the reasons for having them done. Incidentally, I would probably also offer you the progesterone injections again, serially follow your cervix by ultrasound starting at 15-16 weeks,and periodically evaluate you for evidence of asymptomatic urinary tract and vaginal infections until you got past 28 weeks.

Best of luck to you and please let us know what is found, what you do, and how things turn out!
Dr T

Labels: 17-hydroxyprogesterone caproate, cerclage, cervical incompetence, midtrimester pregnancy loss, preterm labor

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"A Stitch in Time..."

Today, let’s take a break from my ‘lecture series’ on preterm birth and present a real-life patient who illustrates a scenario in which experience, technology, and timely intervention averted a tragic pregnancy outcome from PTB…

Recently, we helped care for a woman carrying twins conceived by in vitro fertilization. She had a long history of infertility associated with polycystic ovary syndrome (PCOS) and at age 38 had all but given up hope of ever carrying a pregnancy. Our infertility group, and her primary obstetrician, had sent her to us for consultation at 12 weeks’ because of her age and the multiple gestation. She had no other significant medical problems and the discussion was very straightforward. We talked about PCOS-associated risks of hypertensive disorders and gestational diabetes and we also talked about the age-related risks of fetal chromosomal abnormalities and her options for prenatal diagnosis. She was well-educated and there was little new information I could provide her with on these topics.

We then talked about fetal complications specific to twin pregnancies and finally we got around to the subject of preterm labor. In brief, I informed her that she was at greater risk for PTB, not only because of the twins, and this being her first pregnancy, but also because of her underlying PCOS for reasons that are poorly understood and unrelated to any other medical complications either she or the twins might develop during the pregnancy. My specific concern was related to a condition called “cervical incompetence” that seems to haunt infertility patients with PCOS. Of all the things we discussed, this worried her the most. After all the time (and money) it had taken to conceive, the last thing she wanted was “to deliver too early and at my age have children who have problems resulting from prematurity.” When she left that day, I scheduled her to return at about 20 weeks’ for ultrasound evaluation of the babies and her cervix.

Cervical incompetence represents loss of integrity at the internal cervical os (the junction of the cervix and the uterus) that results in progressive cervical change from the inside out. Lots of factors can contribute to cervical incompetence and we will save that discussion for another day. Before the availability of ultrasound, however, the diagnosis was almost never made before a woman had delivered prematurely, or lost one or more pregnancies, with a history of 'silent' cervical dilation, usually presenting in the advanced stages of labor, preceded by minimal painful contractions. Over the last 10 years, we have learned that ultrasound evaluation of cervical length and configuration can help to identify cervical incompetence and certain women at increased risk for premature delivery.

When our patient came back at 20 weeks,’ her baby girl and boy looked fine. Her cervix measured 42 mm in length (very good!) but “slight funneling is noted at the internal cervical os.” No cause for immediate concern or action, but with that finding, she did buy herself a follow up ultrasound. Although scheduled for the next week, she could not keep that appointment. When she did return two weeks later, she now had “U-shaped funneling of membranes in the cervical canal to within 3 mm of the external cervical os” (very BAD!). To make a long story short, she was admitted to the hospital that day and underwent placement of an emergency (“rescue”) cervical cerclage (stitch around the cervix). At the time of the surgery, “the cervix was 1-2 cm dilated and membranes were clearly visible just within the cervix.” If something had not been done at that point, she surely would have delivered extremely prematurely, probably within days. Although the surgery went well, she understood that she still wasn’t out of the woods for early delivery and complications, especially those related to infection.

There is a happy ending to this story. She eventually carried the babies to 36 weeks’ before spontaneously rupturing membranes, having the cerclage removed, and delivering two beautiful healthy children who got to leave the hospital with her two days later. Technically, she had two “near term” births, but that was so much better than losing two babies at 22 weeks or, perhaps even worse, having two babies survive at 23-24 weeks with severe sequelae secondary to their prematurity. Like I said before, in the case of PTB, every little bit helps. Multiple factors contribute to PTB, but the key to reducing rates is to successfully anticipate risks and identify specific factors in individuals that might lend themselves to timely intervention.

Labels: cerclage, cervical incompetence

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