Friday, April 28, 2017

Miscarriages

A friend asks about miscarriages. For what it's worth, here's my response:

  1. Definitions

    a. Miscarriage is also known as spontaneous abortion. Spontaneous abortion probably isn't the best term because it could confuse people to think it's associated with elective abortion.

    b. Miscarriage is such a broad term. In general it refers to a pregnancy that spontaneously ends before the embryo or fetus has reached a viable gestational age. Although a further complication is "viable gestational age" is itself a vague term susceptible to change (e.g. depending on medical science and technology). Currently that would be around the 20th week of gestation (as calculated from the date of the last menstrual period).

    c. Another common definition of miscarriage (such as the World Health Organization uses) is the spontaneous expulsion of an embryo or fetus weighing 500 g or less. A 500 g fetus would approximately correspond to the 20th week of gestation.

    d. Miscarriages can be subdivided into complete or incomplete miscarriages. If it's complete, then the uterus is entirely emptied, whereas if it's incomplete, then some tissue remains.

    e. One could make further distinctions such as induced (usually elective) abortions, threatened abortions, inevitable abortions, missed abortions, and tubal abortions or ectopic pregnancies.

  2. Incidence

    a. It's somewhat difficult to obtain accurate numbers (e.g. depending on how miscarriages are detected).

    b. At least to my knowledge, most of these studies on miscarriages are based on tests measuring β-hCG. But measuring β-hCG has its limitations. Other tests measure other factors like early pregnancy factor (EPF), but these tests may have their limitations too.

    c. What is the incidence of spontaneous abortions or miscarriages? Estimates range from 8-20% of all clinically recognized pregnancies under 20 weeks and 13-26% if we include unrecognized pregnancies.

  3. Etiology

    a. The most common cause of spontaneous abortions is most likely due to genetic abnormalities in the embryo or fetus. This is thought to account for -75% of all spontaneous abortions. The most common genetic abnormalities are autosomal trisomies (50% of all genetic abnormalities) - and trisomy 16 (which is 100% lethal) is the most common of the trisomies.

    b. Other causes of spontaneous abortions (~25%) are infections, autoimmune diseases, endocrine issues, uterine issues, and drug or substance abuse.

  4. Risk factors

    The biggest risk factors for spontaneous abortions are: advanced maternal age, previous spontaneous abortion, and maternal smoking (10 cigarettes per day or more).

  5. Fertilization/conception

    a. I think it's worth noting an important distinction: fertilization is not identical to conception and vice versa. Fertilization occurs when the sperm enters or penetrates the oocyte (later ovum) or egg. Conception occurs when the sperm and egg cease to exist as sperm and egg in order to become a zygote which has its own unique genetic material.

    b. I think it's possible to argue human life begins either at fertilization or conception. I see merits to both. I'd like to say we should play it safe and err on the side of fertilization. And I'd argue conception (syngamy) is certainly the latest it could be.

    c. I realize many or most state the sperm and egg fuse, unite, or the like. That's fine as far as it goes, and I don't object to the terminology. However at certain times it could be misleading language, scientifically speaking. More on this below.

    d. After the sperm has entered the egg, but prior to the creation of the zygote, the sperm and egg duplicate their respective genetic information in becoming paternal pronuclei and maternal pronuclei. The two pronuclei line up and move toward one another within the egg, their nucleic membranes dissolve (not fuse), and the chromosomes pair up to eventually become a new human genome.

    e. Overall it takes approximately 12-18 hours after fertilization for the zygote to be created.

  6. References

    Beckmann, C. Obstetrics and Gynecology (2009). (6th ed.).
    Cunnigham et al. (2014). Williams Obstetrics (24th ed.).
    Mularz, A., Dalati, S., & Pedigo, R. (eds.). (2016). OB/GYN Secrets (4th ed.).
    Tulandi, T., & Al-Forzan, H.M. (2017). "Spontaneous abortion: Risk factors, etiology, clinical manifestations, and diagnostic evaluation". In D. Levine, R. Barbieri, & K. Eckler (eds.), UpToDate. Retrieved April 28, 2017, from https://www.uptodate.com/contents/spontaneous-abortion-risk-factors-etiology-clinical-manifestations-and-diagnostic-evaluation

Friday, April 28, 2017

Miscarriages

A friend asks about miscarriages. For what it's worth, here's my response:

  1. Definitions

    a. Miscarriage is also known as spontaneous abortion. Spontaneous abortion probably isn't the best term because it could confuse people to think it's associated with elective abortion.

    b. Miscarriage is such a broad term. In general it refers to a pregnancy that spontaneously ends before the embryo or fetus has reached a viable gestational age. Although a further complication is "viable gestational age" is itself a vague term susceptible to change (e.g. depending on medical science and technology). Currently that would be around the 20th week of gestation (as calculated from the date of the last menstrual period).

    c. Another common definition of miscarriage (such as the World Health Organization uses) is the spontaneous expulsion of an embryo or fetus weighing 500 g or less. A 500 g fetus would approximately correspond to the 20th week of gestation.

    d. Miscarriages can be subdivided into complete or incomplete miscarriages. If it's complete, then the uterus is entirely emptied, whereas if it's incomplete, then some tissue remains.

    e. One could make further distinctions such as induced (usually elective) abortions, threatened abortions, inevitable abortions, missed abortions, and tubal abortions or ectopic pregnancies.

  2. Incidence

    a. It's somewhat difficult to obtain accurate numbers (e.g. depending on how miscarriages are detected).

    b. At least to my knowledge, most of these studies on miscarriages are based on tests measuring β-hCG. But measuring β-hCG has its limitations. Other tests measure other factors like early pregnancy factor (EPF), but these tests may have their limitations too.

    c. What is the incidence of spontaneous abortions or miscarriages? Estimates range from 8-20% of all clinically recognized pregnancies under 20 weeks and 13-26% if we include unrecognized pregnancies.

  3. Etiology

    a. The most common cause of spontaneous abortions is most likely due to genetic abnormalities in the embryo or fetus. This is thought to account for -75% of all spontaneous abortions. The most common genetic abnormalities are autosomal trisomies (50% of all genetic abnormalities) - and trisomy 16 (which is 100% lethal) is the most common of the trisomies.

    b. Other causes of spontaneous abortions (~25%) are infections, autoimmune diseases, endocrine issues, uterine issues, and drug or substance abuse.

  4. Risk factors

    The biggest risk factors for spontaneous abortions are: advanced maternal age, previous spontaneous abortion, and maternal smoking (10 cigarettes per day or more).

  5. Fertilization/conception

    a. I think it's worth noting an important distinction: fertilization is not identical to conception and vice versa. Fertilization occurs when the sperm enters or penetrates the oocyte (later ovum) or egg. Conception occurs when the sperm and egg cease to exist as sperm and egg in order to become a zygote which has its own unique genetic material.

    b. I think it's possible to argue human life begins either at fertilization or conception. I see merits to both. I'd like to say we should play it safe and err on the side of fertilization. And I'd argue conception (syngamy) is certainly the latest it could be.

    c. I realize many or most state the sperm and egg fuse, unite, or the like. That's fine as far as it goes, and I don't object to the terminology. However at certain times it could be misleading language, scientifically speaking. More on this below.

    d. After the sperm has entered the egg, but prior to the creation of the zygote, the sperm and egg duplicate their respective genetic information in becoming paternal pronuclei and maternal pronuclei. The two pronuclei line up and move toward one another within the egg, their nucleic membranes dissolve (not fuse), and the chromosomes pair up to eventually become a new human genome.

    e. Overall it takes approximately 12-18 hours after fertilization for the zygote to be created.

  6. References

    Beckmann, C. Obstetrics and Gynecology (2009). (6th ed.).
    Cunnigham et al. (2014). Williams Obstetrics (24th ed.).
    Mularz, A., Dalati, S., & Pedigo, R. (eds.). (2016). OB/GYN Secrets (4th ed.).
    Tulandi, T., & Al-Forzan, H.M. (2017). "Spontaneous abortion: Risk factors, etiology, clinical manifestations, and diagnostic evaluation". In D. Levine, R. Barbieri, & K. Eckler (eds.), UpToDate. Retrieved April 28, 2017, from https://www.uptodate.com/contents/spontaneous-abortion-risk-factors-etiology-clinical-manifestations-and-diagnostic-evaluation