today was my much-anticipated visit with dr. s, the man with the power to tell me (or not) that it is ok (or not) to toss out the dreaded rubber sheaths and start seriously thinking about v.4.0

but not before taking my full history (how i love recounting all seven pregnancies) and asking me all kinds of questions that i have always been just as happy not to know about my family’s medical history, and then starting with the ugly stats: given my age alone, things look bleak for a future baby’s chromosomes. as he rattled off percentages (1 in 25-30 chance of conceiving a baby with down’s, for example, and a 1 in 70 chance of delivering a baby with down’s — “because of attrition, you understand”) i kept reminding myself that these stats are no worse than those we learned in 2005 and that all three children i’ve delivered have been chromosomally normal and that it doesn’t make me crazy, not totally anyway, to want another child anyway and in that way i was able to calm myself down and not run screaming from the room. because really, who in their right mind would consider conceiving when your go-to doc is giving such scary news?

yeah, me, that’s who.

soon the scary morphed into the weird. “at this point” says dr s “we’re out hunting for zebras.” maybe, he conjectured, i should be examined for ehlers-danlos syndrome (eds) and marfan syndrome, both syndromes of weakened connective tissues that can affect the cervix (and i suppose, given collagen blah blah blah, can probably also affect the amniotic sac). but the little bit of reading i’ve done suggests to me that i probably do not have even mild variants of either syndrome. yep, i’m tall but not unusually so, and not unusually so within my family. i’m thin, but not extremely. i bruise easily, but then i also walk into doors on a regular basis. my limbs are not long relative to the rest of me. i don’t easily sprain or dislocate my body parts. i am pretty flexible, but not freakishly so. (no future in the cirque du soleil for me.) but since women with the classical type of eds are more prone to premature rupture of the membranes, we will be looking into this. by “we” i mean, of course, the army of doctors i feel i’m about to get real up close and personal with.

as for mthfr. well. for starters he reminds me that it is most closely associated with cardiovascular disease in adults. but then he tells me it’s a non-entity, because it seems that recently it has been de-linked from c-v disease in adults. and if i am homozygous for mthfr then i’ll just take lots of folic acid, and if i’m a decently-fed woman in the united states i’m probably getting enough anyway. (sound familiar? i swear these guys must talk to each other.) but you can bet your booty (pirate or high-and-deep) that i’ll be taking as much folic acid as anybody allows.

and then we got to metalloproteinase-8. ahh, the dreaded enzyme discussion. you know, i felt like there was something here. after all, i read — i read, dammit — that in women with prom the measurements of the stuff were higher than in women without. (remember this, from that medical report that nobody could read…?)

Spontaneous rupture of membranes in preterm gestation but not in term gestation was associated with elevated amniotic fluid concentrations of MMP-8.

so i’m telling dr s about this study and the first thing he does is tell me it doesn’t sound like a clean study (ooh! a dirty study!) and i spend a millisecond wondering why the word “clean” is preferable to the phrase “badly-designed” but he’s moving to talk about the fact that sure, we can test my amniotic fluid for mmp-8 but even if we find it we can’t do anything about it. and then i’ve had an amnio, which brings with it (he did not need to remind me) the 1/4% chance of pregnancy loss.

while in salt lake i’d had to stop at a drugstore for baby tylenol and an ear-thermometer for my getting-sicker-by-the-minute toddler and i saw — da da da dah! — collagen supplements. who knew? and turns out they include vitamin c, which jives with some of the other reading i’ve been doing. so i asked dr s about taking collagen supplements and, good researcher that he is, he told me he can’t give me an opinion because he doesn’t know anything about their efficacy. he did suggest (strongly) that if i’m going to take them i bring the bottle to him or dr l so they can determine whether the pills include anything that will do additional harm. as i was listening to him tell me this i just kept thinking “i bet he says a version of that to all his patients who want to use homeopathic remedies” and found myself wondering if he’d think those patients are weird (i always assume they will but am looking forward to being proved wrong).

and then a new piece of news: part of ruby’s placenta’s pathology describes our placenta as having “perivillous fibrin deposition” which means, he said, that for my next pregnancy i would be on baby aspirin and heparin. this surprised me. he told me that most people assume heparin is the important treatment, but studies suggest that the two are most successful together. baby aspirin with earl. heparin with mairin. heparin with ruby. heparin and baby aspirin with v.4.0 it is. (for some good scary reading, google perivillous fibrin deposition and maternal floor infarction. and stay away from the pictures.)

but the best news of all: there is no need (save “old wives’ tales” — or, as dr s corrected himself, “old obs’ tales”) to wait for three periods. the purpose of waiting is to give the uterus a chance to clean itself out — to build and shed and build and shed the endometrium so that that yummy-sticky-jam-sandwich of a lining is all fresh. but he said two periods would be as good as three. and period #2 is due in about 6 days. (how do i know? poor s is already running for cover when i walk in the door, that’s how.)

so the upshot: we do a little more medical workup but nothing that needs to happen pre-conception. and, oooh, it will be nice to remember how fun unencumbered sex can be.

as for the zebras: dr s may be hunting for them, but as s says it doesn’t matter whether we find one. it only matters that we shoot the lion before he kills it.

“Midtrimester amniotic fluid matrix metalloproteinase-8 (MMP-8) levels above the 90th percentile are a marker for subsequent preterm premature rupture of membranes.”

Abstract: Objective: We sought to determine whether midtrimester amniotic fluid levels of matrix metalloproteinase-8 were associated with subsequent preterm premature rupture of membranes.Study design: We conducted a case-control study examining 57 asymptomatic women who underwent genetic amniocentesis from 14 to 21 weeks’ gestation and subsequently had preterm premature rupture of membranes (<35 wk) and 58 women with subsequent term delivery. Measurement of total matrix metalloproteinase-8 level in amniotic fluid was conducted using a commercially available enzyme-linked immunosorbent assay and association with preterm birth due to preterm premature rupture of membranes was assessed. Results: The overall distribution of matrix metalloproteinase-8 concentrations was similar in women who had preterm premature rupture of membranes and term controls (median 2.39 ng/mL, 25th to 75th percentile 1.1-10.1 vs 2.37 ng/mL, 25th to 75th percentile 1.5-4.7, P=.94). However, 26% of women who had preterm premature rupture of membranes had a matrix metalloproteinase-8 concentration above the 90th percentile (8.7 ng/mL), compared with only 10% of term controls (odds ratio 3.1, 95% CI 1.1-8.7; P=.03). Elevated matrix metalloproteinase-8 remained associated with preterm premature rupture of membranes after adjustment for maternal age, race, parity, gestational age, and year of amniocentesis (odds ratio 3.4, 95% CI 1.2-9.9; P=.03). Conclusions: The overall distribution of midtrimester amniotic fluid matrix metalloproteinase-8 levels did not differ between women who had preterm premature rupture of membranes and those delivered at term. However, marked elevations of midtrimester amniotic fluid matrix metalloproteinase-8 were highly associated with subsequent preterm premature rupture of membranes, suggesting that the pathophysiologic processes that contribute to preterm premature rupture of membranes may begin in early pregnancy.

and this:

Human neutrophil collagenase (matrix metalloproteinase 8 ) in parturition, premature rupture of the membranes, and intrauterine infection

MAYMON E.; ROMERO R.; PACORA P.; GOMEZ R.; ATHAYDE N.; EDWIN S.; YOON B. H.

Perinatology Research Branch, National Institute of Child Health and Human Development, ETATS-UNIS
Department of Obstetrics and Gynecology, Wayne State University/Hutzel Hospital, ETATS-UNIS
Department of Obstetrics and Gynecology, Seoul National University, COREE, REPUBLIQUE DE

OBJECTIVES: The mechanisms by which microbial invasion of the amniotic cavity leads to membrane weakening and rupture are poorly understood. Recently, endogenous host enzymes have been implicated in this process. Matrix metalloproteinases are a family of potent enzymes that degrade components of the extracellular matrix. Collagen type I provides the main tensile strength of the fetal membranes. Matrix metalloproteinase 8 (MMP-8), or neutrophil collagenase, degrades interstitial collagens, acting preferentially on collagen type I. This study was undertaken (1) to determine whether MMP-8 is present in amniotic fluid and whether its concentrations are changed in preterm and term labor and membrane rupture with and without intra-amniotic infection and (2) to determine whether the amniotic fluid concentrations of MMP-8 in labor at term are different in the lower and upper uterine compartments. STUDY DESIGN: A cross-sectional study was conducted and transabdominal amniocentesis was performed in women in the following categories: (1) midtrimester (n = 25), (2) preterm labor in the presence and absence of microbial invasion of the amniotic cavity (n = 86), (3) preterm premature rupture of the membranes in the presence and absence of microbial invasion of the amniotic cavity (n = 51), (4) term patients in labor and not in labor (n = 51), and (5) term premature rupture of membranes (n = 20). Additional paired samples of amniotic fluid were retrieved by transabdominal amniocentesis (upper compartment) and transvaginal amniocentesis (lower or forebag compartment) from 14 term patients (28 samples) in spontaneous labor with intact membranes. Amniotic fluid MMP-8 concentrations were determined with a sensitive and specific immunoassay. RESULTS: MMP-8 was detected in 95.4% (249/261) of all samples. (1) Spontaneous human parturition was associated with a significant increase in amniotic fluid concentrations of MMP-8 in both term and preterm gestation. Term (no labor median, 3.3 ng/mL; range, <0.06-38.6 ng/mL; vs labor median, 16.6 ng/mL; range, 0.33-1650 ng/mL; P <.05). Patients with preterm labor who delivered preterm (in the absence of microbial invasion of the amniotic cavity) had a significantly higher median amniotic fluid MMP-8 concentration than those with preterm labor who delivered at term (preterm labor, term delivery median, 3.1 ng/mL; range, <0.06-415.1 ng/mL; vs preterm labor, preterm delivery median, 32.5 ng/mL; range, <0.06-6006.6 ng/mL; P <.003). (2) Spontaneous rupture of membranes in preterm gestation but not in term gestation was associated with elevated amniotic fluid concentrations of MMP-8. Preterm gestation (preterm labor, intact membranes median, 3.1 ng/mL; range, <0.06-415.1 ng/mL; vs preterm premature rupture of membranes median, 35.1 ng/mL; range, 0.71-1184.1 ng/mL; P <.05). Term gestation (intact membranes median, 3.3 ng/mL; range, 0.24-38.6 ng/mL; vs rupture of membranes median, 5.6 ng/mL range, 0.22-19.8 ng/mL; P =.9). (3) Microbial invasion of the amniotic cavity was associated with a significant increase in amniotic fluid MMP-8 concentration in patients with preterm labor and intact membranes, as well as in patients with preterm premature rupture of membranes. Preterm labor (no microbial invasion of the amniotic cavity, preterm delivery median, 32.5 ng/mL; range, <0.06-6006.6 ng/mL; vs microbial invasion of the amniotic cavity median, 208.1 ng/mL; range, 4.2-14,600 ng/mL; P<.001).

American journal of obstetrics and gynecology (Am. j. obstet. gynecol.) ISSN 0002-9378 CODEN AJOGAH

and a bit of help from wikipedia, on “metalloproteinase”:

The collagenases are capable of degrading triple-helical fibrillar collagens into distinctive 3/4 and 1/4 fragments. These collagens are the major components of bone and cartilage, and MMPs are the only known mammalian enzymes capable of degrading them. Traditionally, the collagenases are #1, #8, #13, and #18. In addition, #14 has also been shown to cleave fibrillar collagen, and more controversially there is evidence that #2 is capable of collagenolysis. In MeSH, the current list of collegenases includes #1, #2, #8, #9, and #13. #14 is present in MeSH but not listed as a collegenase, while #18 is absent from MeSH.

so now i know that there may be a genetic factor (mthfr) and/or a physiological factor (the proteinases are enzymes) at work. the genetic factor can be tackled by folic acid. but the enzymes? no idea. must ask more about collagen structure and ways to strengthen it. and about enzyme testing — if such a thing exists and/or is possible — and at what stage.

the most interesting tidbit i gleaned while reading is that amniotic fluid is typically without white blood cells, so any response to infection (maybe only if the sac hasn’t broken? that makes sense, but i don’t actually know) comes from the baby. it’s such an interesting glimpse  into the mother/baby relationship during gestation.