hx of HELLP with donor sperm, MTHFR, protein C

[expert@preeclampsia.org]

I’m a 37y.o. G1P0. I developed severe preeclampsia and HELLP syndrome (Class 1) at 23w1d which immediately led to an emergency cesarean section (classical incision). My son died 4 hours after he was born. My husband and I are planning to try to conceive again; we were advised to wait until 6 months after my C/S.

For a bit of background information, my risk factors for preeclampsia were being a nulligravida, advanced maternal age (36y at time of conception), and donor insemination. We successfully conceived on our 3rd IUI with frozen sperm from a donor. The pregnancy was also complicated by new onset severe migraine headaches and an abnormal 2nd trimester screen suggesting a 1/29 risk for Down Syndrome; the amniocentesis results were normal. We have since consulted with an MFM specialist and the thrombophilia workup revealed a Protein C deficiency and heterozygosity for the MTHFR DNA mutation (A1298C). Otherwise I’m a very healthy person; my medical history is only significant for the occasional bout of Raynaud’s phenomenon and tension headaches.

I understand that you cannot provide specific medical advice about individual cases, but I would appreciate it if you would consider the following questions:

1.) Should the same or different sperm donor be used in future conception attempts?

The literature seems to suggest a possible immunological role of donor insemination and preeclampsia. And I would obviously like to reduce my risk for recurrence as much as possible. Unfortunately, I have heard mixed opinions regarding this issue. One OB/GYN has said use the same donor; another said use a different donor. And, the specialist indicated that there is not enough evidence to base an opinion for or against using the same donor. If ‘some’ evidence suggests that increased exposure to a partner’s sperm decreases the risk of preeclampsia, should the same donor be used in future conception attempts?

2.) When should anticoagulation begin if you have an inherited thrombophilia?

It has been suggested that anticoagulation with Lovenox be initiated as soon as there is a positive pregnancy test. I am curious whether any evidence suggests benefits of anticoagulation at the time of or just prior to conception – such as with low dose Aspirin—as compared to starting anticoagulation roughly 2 weeks later with a positive pregnancy test. Another approach I heard about it is a combination of the above: start ASA when you are trying to conceive and then switching to Lovenox once there is a positive pregnancy test. What does the evidence suggest?

Thank you for your time, dedication to this issue, and any information you can share!!

[expert@preeclampsia.org]

Recurrence risk for HELLP-severePRE at <28 weeks gestation is estimated to be at least 50% under most circumstances.

The literature is conflicted on the donor sperm issue as I interpret it--there is not a certain answer. Latest data from Belgium (Fertil Steril 2009 Feb 14 epub, Kyrou et al) indicates that donor sperm increases chance of PRE, multiple cycles "protective" suggesting to me that same donor might be preferable (but the mother's genes are probably more important than the father's).

Interval of time between pregnancies is best at 12-18 months and not less, especially with prior classical (time to heal).

Personally I avoid anticoagulants in first trimester due to bleeding problems unless absolutely needed; your MFM must assess degree of protein C deficiency as possibly use prophylactic dosing of heparin or Lovenox--wait until gestation established for 10-12 weeks.

Raynaud's is connected to pulmonary hypertension in the mother, so echo heart for baseline is prudent (not well known).

I assume antiphospholipid antibodies and lupus anticoagulant are within normal limits. Low dose aspirin would be recommended in my practice to start now before pregnancy to carry you through. Superb nutrition is probably desirable.