Patients with at least one loss characterized as euploid (genetically normal) have an outstanding 78% chance of having a baby at BRI. A review of 90 cases at Braverman IVF & Reproductive Immunology

The literature confirms that women with euploid losses have a higher risk of recurrent loss if not treated.

We previously reported a high success rate in women with a history 5 or more miscarriages-80% (a group with high probability of euploid losses). We now report on a larger series of women with a history of at least one euploid loss, a group of patients that most likely have immune related implantation issues.

First results of our retrospective study based on 90 cases under our care showed a live birth rate of 77.8% as seen in Figure 1 (p=.0001, a very low p value shows a very high statistical significance).

Figure 1: Live birth rate at Braverman Reproductive Immunology in women with at least 1 euploid loss and after adequate immune therapies.(This is not a guarantee of future performance).

There was no significant difference between the different types of infertility as shown in Figure 2.

• Primary has no history of a successful birth prior to the miscarriages
• Secondary has a history of a full term birth followed by miscarriages
• Tertiary has a history of miscarriages prior to and after a full term birth

Figure 2: Live birth rate at Braverman Reproductive Immunology in women with at least 1 euploid loss and after adequate immune therapies based on the type of infertility.

Now, if we consider only the first attempt to conceive, 71% of our patients will get a successful pregnancy as seen in Figure 3 (p=.0001, a very low p value shows a very high statistical significance).

Figure 3: Live birth rate at Braverman Reproductive Immunology at first attempt in women with at least 1 euploid loss and after adequate immune therapies.

We defined euploid losses as pregnancies losses with:

• aCGH on the product of conception (POC) showing euploid (normal) karyotype
• Normal PGD (Preimplantation genetic diagnosis) tested embryo with a fetal heartbeat (FHB) detected prior to the loss
• Clinical pregnancy (>6 weeks) with a FHB detection prior to the loss

ALL patients who had immune work done with us were included in the study with the ONLY exclusion being uterine anomalies. Patients received our tailored immune therapy based on their results prior to conception (natural conception or IVF cycle), and the treatment was maintained at least through the first trimester.
The pregnancy outcome was recorded retrospectively with a successful pregnancy being defined as a live birth or an ongoing pregnancy of more than 20 weeks.

As discussed in our previous blog on women with at least 5 losses (add the link), women with euploid losses are at higher risk for further losses. Patients with a history of aneuploidy miscarriages (abnormal genetics) , do not appear to be at increased risk for recurrent losses.

1- Review of the current literature on recurrent pregnancy loss statistics.

a. Ogasawara and collaborators¹

They showed that the likelihood of a loss being normal (euploid) was higher in recurrent miscarriage patients (48.7%) compared to the control population of those having a miscarriage for the first time (23.7%).
Interestingly, the frequency of an aneuploid (abnormal) loss significantly decreased with the number of previous miscarriages, while that of a normal loss (euploid) significantly increased. Showing a likely cause and not just a random one.

b. Morikawa and collaborators²

They showed that RPL patients are more prone to have another euploid loss confirming these results.
In this study, euploid losses were shown to be significantly higher in RPL patients (66.7%) vs. controls (45.7%) while aneuploid losses remain the same between the two groups. Again this shows that it is the euploid losses that most likely need treatment.

c. Carp and collaborators³

They focused on genetic testing on products of conception in patients with 3 or more miscarriages. They found that the incidence of aneuploid losses among these miscarriages was 29% while 71% of losses were euploid. They also estimated that after an aneuploid loss, 68% will have a live birth while after euploid losses only 41% will have a live birth.

Altogether these data clearly show that patients with high number of miscarriages are most likely to lose euploid pregnancies and these types of losses tend to reoccur without treatment.

1. Comparing our success at BRI against the published literature

Figure 5: Pregnancy success rate at Braverman Reproductive Immunology in comparison with other relevant studies.

a- The Ogasawara study¹

In their study, Ogasawara and collaborators included a large set of patients with RPL (n=1309) who had between 2 and 20 consecutive first trimester losses before a subsequent pregnancy¹. They did not select for euploid losses as we did here at BRI and still had exclusions in their study where we had none.

Immune therapy was administrated to patients with at least 3 prior pregnancy losses.
In their study, 65% of RPL patients (2 or more losses) managed to have a successful pregnancy, with treatment compared to 77.8% for our patients here at Braverman Reproductive Immunology. When considering patients with at least 5 losses, they have a 35% success compared to 80% for us at BRI. The pregnancy success rate should have been higher and the number of euploid losses (49%) should have been lower if the therapy was appropriate.

b- The Morikawa study²

In this study, the authors studied 75 cases of RPL patients with at least 2 prior losses. They found that 38% would have a successful pregnancy compared to 78% for our treated patients here at Braverman Reproductive Immunology. And most of the losses in their study (67%) are euploid showing again that the therapies that they provided were inadequate and/or inefficient to sustain a euploid pregnancy

c- Where do we stand in comparison with other reports?

We had a higher overall pregnancy success rate in patient with one or more euploid losses compared to both Ogasawara (p=.01) and Morikawa studies (p=.0001). At first attempt to conceive, we had71% of pregnancy success as shown in Figure 5 and we have to highlight that our overall pregnancy success rate of 77.8% is reached with a maximum of three attempts.
In patients with < 5 losses,our pregnancy success rate reaches the outstanding value of 80%, that is much higher than Ogasawara study (p=.0001, low p value shows a high statistical significance).
This shows that our immune therapies are highly adapted and effective in retaining euploid pregnancies.

References

1. Ogasawara M, Aoki K, Okada S, Suzumori K. Embryonic karyotype of abortuses in relation to the number of previous miscarriages. Fertil Steril. 2000 Feb; 73(2):300-4. PubMed PMID: 10685533.
2. Morikawa M, Yamada H, Kato EH, Shimada S, Yamada T, Minakami H. Embryo loss pattern is predominant in miscarriages with normal chromosome karyotype among women with repeated miscarriage. Hum Reprod. 2004 Nov; 19(11):2644-7.
3. Carp H, Toder V, Aviram A, Daniely M, Mashiach S, Barkai G. Karyotype of theabortus in recurrent miscarriage. Fertil Steril. 2001 Apr; 75(4):678-82.