This is a post I've been meaning to write since my last ob visit.
My Ob was not wild about me staying on metformin at our first appointment. I think I'm probably the first patient she's had come to her after conceiving on metformin and whole heartedly wanting to stay on it.
First, I just want to say that met was one of the best things that has ever happened to me. I love it. I don't think I'd be pregnant right now with out it. When I started it, it was like I was a new person. The spark came back into my life again. I had energy. For the first time (in a long time) I actually felt the effects of adding the calories into my body. And it never mattered how well I dieted before, they just didn't work, I couldn't loose weight without massive amounts of exercise. But since the met, I have been eating sensibly and loosing weight like a normal person does (amazing). I didn't really have any digestive issues other than a little extra gas (really only lasted for the first 6 weeks). I really like my dosage- 750mg Extended Release twice daily. If you feel a little knocked around/light headed on met, I highly recommend you try extended release. If you have digestive problems, see if going low carb helps while your body adjusts.
But back to pregnancy and met... my Ob wasn't sure and we decided to discuss it again at my 13 week appt and she would pull some research to review before then. And I pulled some research of my own of course.
First, check out Bird's list of papers on met during pregnancy. Their are some excellent papers listed there. And I have a few more papers listed below too.
Basically, when me and my Ob met again at my 13 week appt. she had read enough and knew that I was well informed on the risks and had read the research to support me in this. Neither she nor I had seen any research indicating complications from using it. HOWEVER, the research is not complete. There needs to be more, larger, long term studies showing the safety of metformin during pregnancy. Both she and I agree on that. But, I have weighed the research and am comfortable taking that risk because the benefits appear to outweigh the risk at this time. And she agrees with me and is going to support me in this decision.
In general, women with PCOS tend to face a significantly higher risk of complications during pregnancy (including miscarriage, preeclampsia, and gestational diabetes, to name a few). In comparing control groups (non pcos women) to pcos women on placebo and pcos women on met, the risks of these complications tend to be significantly reduced to levels meeting or even exceeding those of the non pcos women (even when controlling for weight). I haven't seen any reported increases of congenital defects from taking met. The last study on here shows that children of women who took met during pregnancy show no signs of abnormal development at 18 months.
The first and second papers on my list appear to conflict on whether met decreases in utero exposure to testosterone. If it does decrease exposure to testosterone, that is something really interesting to consider. PCOS appears to be an inherited condition... but no one has been able to determine if it is genetic yet. Also, PCOS symptoms can appear so differently between women... so what if exposing baby girls excess testosterone in the womb is a factor contributing to the development of PCOS? I'm just pulling this out of my ass, but wouldn't it be incredible if they determined that in utero exposure to testosterone causes PCOS 5 or 10 years from now, and this cheap and widely available drug prevents your daughter from developing it? How great would that be? But this is just Amanda's wishful thinking brain here and not really based on scientific facts at all (but it makes you think).
Conversely, if 10 years from now, they determine that kids exposed to met in the womb all develop type II diabetes at 13 that would not be good at all. I am taking a gamble here, and I hope I don't loose.
Well, if you are TTC and on met, I really recommend that you do some research. Stick to peer reviewed papers in actual journals and don't just believe the crap on blogs (particularly this one) or in chat rooms.
Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout pregnancy
C.J. Glueck , N. Goldenberg , P. Wang , M. Loftspring , and A. Sherman
Hum. Reprod. Advance Access published on March 1, 2004, DOI 10.1093/humrep/deh109.
Hum. Reprod. 19: 510-521.
BACKGROUND: In a prospective observational study of 42 pregnancies in 39 Caucasian women (age 30 ± 4 years) with polycystic ovary syndrome (PCOS), we examined effects of metformin on maternal insulin, insulin resistance (IR), insulin secretion (IS), weight gain, development of gestational diabetes (GD), testosterone and plasminogen activator inhibitor activity. We assessed the hypothesis that diet–metformin (MET) lessens the physiological gestational increase in IR and reduces gestational weight gain, thus reducing GD. METHODS: Preconception, in an out-patient clinical research centre, MET 1.5 (eight pregnancies) to 2.55 g/day (34 pregnancies) was started. Women with body mass index <25 or 25 kg/m2 were given a 2000 or 1500 calorie/day, high-protein (26% of calories), low-carbohydrate (44%) diet. Calorie restrictions were dropped after conception. RESULTS: On MET, GD developed in three out of 42 pregnancies (7.1%). Median entry weight (94.5 kg) fell to 82.7 on MET at the last preconception visit (P = 0.0001), fell further to 81.6 during the first trimester, was 83.6 in the second trimester, and 89.1 kg in the third trimester. Median weight gain during pregnancy was 3.5 kg. The median percentage reduction in serum insulin was 40% on MET at the last preconception visit; insulin did not increase in the first or second trimesters (P > 0.05), and rose 10% in the third trimester. The median percentage reduction in HOMA IR was 46% on MET at the last preconception visit; IR did not increase (P > 0.05) in the first, second or third trimesters. HOMA insulin secretion fell 45% on MET at the last preconception visit, did not increase in the first trimester, rose 24% in the second trimester, and rose 109% in the third trimester. Testosterone fell 30% on MET at the last preconception visit (P = 0.01) and then rose 74, 61 and 95% during trimesters 1, 2 and 3; median testosterone during the third trimester did not differ from pre-treatment levels. CONCLUSIONS: By reducing preconception weight, insulin, IR, insulin secretion and testosterone, and by maintaining these insulin-sensitizing effects throughout pregnancy, MET–diet reduces the likelihood of developing GD, and prevents androgen excess for the fetus.
Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study
E. Vanky , K.Å. Salvesen , R. Heimstad , K.J. Fougner , P. Romundstad , and S.M. Carlsen
Hum. Reprod. Advance Access published on August 1, 2004, DOI 10.1093/humrep/deh347.
Hum. Reprod. 19: 1734-1740.
BACKGROUND: Investigation of a possible effect of metformin on androgen levels in pregnant women with polycystic ovary syndrome (PCOS). METHODS: A prospective, randomized, double-blind, placebo-controlled pilot study was conducted. Forty pregnant women with PCOS received diet and lifestyle counselling and were randomized to either metformin 850 mg twice daily or placebo. Primary outcome measures were changes in serum levels of dehydroepiandrosterone sulphate, androstenedione, testosterone, sex hormone-binding globulin, and free testosterone index. Secondary outcome measures were pregnancy complications and outcome. Two-tailed t-tests and 2-tests were used. RESULTS: Maternal androgen levels were unaffected by metformin treatment in pregnant women with PCOS. While none of the 18 women in the metformin group experienced a severe pregnancy or post-partum complication, seven of the 22 (32%) women experienced severe complications in the placebo group (P=0.01). CONCLUSIONS: Metformin treatment did not reduce maternal androgen levels in pregnant women with PCOS. In the metformin-treated group we observed a reduction of severe, pregnancy and post-partum complications. Metformin treatment of pregnant PCOS women may reduce complications during pregnancy and in the post-partum period.
Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin
Charles J. Glueck , Ping Wang , Naila Goldenberg , and Luann Sieve-Smith
Hum. Reprod. 17: 2858-2864.
BACKGROUND: We sought to determine whether metformin, which had facilitated conception in 72 oligoamenorrhoeic women with polycystic ovary syndrome (PCOS), would safely reduce the rate of first trimester spontaneous abortion (SAB) and increase the number of live births without teratogenicity. METHODS: Seventy-two oligoamenorrheic women with PCOS conceived on metformin (2.55 g/day). They were prospectively assessed in an outpatient clinical research centre. Outcome measures included number of first trimester SAB, live births, normal ongoing pregnancies 13 weeks, gestational diabetes (GD), congenital defects (CD), birthweight and height, as well as weight, height, and motor and social development during the first 6 months of life. RESULTS: Of the 84 fetuses, to date there have been 63 normal live births without CD (75%), 14 first trimester SAB (17%), and seven ongoing pregnancies 13 weeks with normal sonograms without CD (8%). Previously, without metformin, 40 of the 72 women had 100 pregnancies (100 fetuses) with 34 (34%) live births and 62 (62%) first trimester SAB. In current pregnancies on metformin in these 40 women (46 pregnancies, 47 fetuses), there have been 33 live births (70%), two pregnancies ongoing 13 weeks (4%), and 12 SAB (26%) (P < 0.0001). There was no maternal lactic acidosis, and no maternal or neonatal hypoglycaemia. Fasting entry serum insulin was a significant explanatory variable for total (previous and current) first trimester SAB, odds ratio 1.32 (for each 5 µU/ml rise in insulin), 95% CI 1.09–1.60 (P = 0.005). On metformin, GD developed in 4% of pregnancies versus 26% of previous pregnancies without metformin, P = 0.025. There have been no major CD in the 63 live births or CD by sonography in the seven fetuses 13 weeks. In the 63 live births, neither weight nor height differed from the normal neonatal population. At 6 month follow-up, height was greater (P = 0.008) and weight did not differ from the normal paediatric population; motor and social development were normal. CONCLUSIONS: Metformin therapy during pregnancy in women with PCOS was safely associated with reduction in SAB and in GD, was not teratogenic, and did not adversely affect birthweight or height, or height, weight, and motor and social development at 3 and 6 months of life.
Height, weight, and motor–social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy
C.J. Glueck , N. Goldenberg , J. Pranikoff , M. Loftspring , L. Sieve , and P. Wang
Hum. Reprod. Advance Access published on June 1, 2004, DOI 10.1093/humrep/deh263.
Hum. Reprod. 19: 1323-1330.
BACKGROUND: We prospectively assessed growth and motor–social development during the first 18 months of life in 126 live births (122 pregnancies) to 109 women with polycystic ovary syndrome (PCOS) who conceived on and continued metformin (1.5–2.55 g/day) through pregnancy. METHODS: The lengths and weights of PCOS neonates were compared with gender-specific Centers for Disease Control and Prevention (CDC) infant data. Gestational diabetes (GD) and pre-eclampsia in women with PCOS were compared with 252 healthy women without PCOS who had 1 live birth (262 live births). RESULTS: There were 101 out of 126 (80%) term (37 gestational weeks) PCOS births, which was not significantly different (P = 0.7) from controls, 206 out of 252 (81.7%). There were two (1.6%) birth defects. GD occurred in nine out of 119 PCOS pregnancies (7.6%) versus 40 out of 251 (15.9%) controls, P = 0.027. The prevalence of pre-eclampsia did not differ in PCOS versus control pregnancies (4.1 versus 3.6%, P = 0.8). The birth length and weight of the 52 male neonates did not differ (P > 0.05) from those of CDC males; the 74 female neonates were shorter than CDC females (48.9 ± 5.4 versus 50.6 ± 2.7 cm, P = 0.006) and weighed less (3.09 ± 0.85 versus 3.29 ± 0.52 kg, P = 0.04). There were no systematic differences in growth between PCOS and CDC infants over 18 months. At 3, 6, 9, 12 and 18 months, of a potential 100% motor–social development score, scores (±SD) were 95 ± 13, 98 ± 8%, 95 ± 10, 97 ± 8 and 94 ± 16%; no infants had motor–social developmental delays. CONCLUSIONS: Metformin reduced development of GD, was not teratogenic and did not adversely affect birth length and weight, growth or motor–social development in the first 18 months of life.
Glueck has probably been the leader in researching metformin in PCOS women and here is a handy link to most of Glueck's research if you would like to read more.