Intent to treat analysis of in vitro fertilization and preimplantation genetic screening versus expectant management in patients with recurrent pregnancy loss.
In an intent to treat analysis, are clinical outcomes improved in recurrent pregnancy loss (RPL) patients undergoing IVF and preimplantation genetic screening (PGS) compared with patients who are expectantly managed (EM)?



Among all attempts at PGS or EM among RPL patients, clinical outcomes including pregnancy rate, live birth (LB) rate and clinical miscarriage (CM) rate were similar.



The standard of care for management of patients with RPL is EM. Due to the prevalence of aneuploidy in CM, PGS has been proposed as an alternate strategy for reducing CM rates and improving LB rates.



Retrospective cohort study of 300 RPL patients treated between 2009 and 2014.



Among two academic fertility centers, 112 RPL patients desired PGS and 188 patients chose EM. Main outcomes measured were pregnancy rate and LB per attempt and CM rate per pregnancy. One attempt was defined as an IVF cycle followed by a fresh embryo transfer or a frozen embryo transfer (PGS group) and 6 months trying to conceive (EM group).



In the IVF group, 168 retrievals were performed and 38 cycles canceled their planned PGS. Cycles in which PGS was intended but cancelled had a significantly lower LB rate (15 versus 36%, P = 0.01) and higher CM rate (50 versus 14%, P < 0.01) compared with cycles that completed PGS despite similar maternal ages. Of the 130 completed PGS cycles, 74% (n = 96) yielded at least one euploid embryo. Clinical pregnancy rate per euploid embryo transfer was 72% and LB rate per euploid embryo transfer was 57%. Among all attempts at PGS or EM, clinical outcomes were similar. Median time to pregnancy was 6.5 months in the PGS group and 3.0 months in the EM group.



The largest limitation is the retrospective study design, in which patients who elected for IVF/PGS may have had different clinical prognoses than patients who elected for expectant management. In addition, the definition of one attempt at conception for PGS and EM groups was different between the groups and can introduce potential confounders. For example, it was not confirmed that patients in the EM group were trying to conceive for each month of the 6-month period.



Success rates with PGS are limited by the high incidence of cycles that intend but cancel PGS or cycles that do not reach transfer. Counseling RPL patients on their treatment options should include not only success rates with PGS per euploid embryo transferred, but also LB rate per initiated PGS cycle. Furthermore, patients who express an urgency to conceive should be counseled that PGS may not accelerate time to conception.



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Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, CA 94305, USA gm807@stanford.edu.
Gayathree
G
Murugappan
Pacific NW Fertility and IVF Specialists, 1101 Madison Street, Suite 1050, Seattle, WA 98104, USA.
Lora K
LK
Shahine
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, CA 94305, USA.
Candice O
CO
Perfetto
Pacific NW Fertility and IVF Specialists, 1101 Madison Street, Suite 1050, Seattle, WA 98104, USA.
Lee R
LR
Hickok
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, CA 94305, USA.
Ruth B
RB
Lathi
D000026:Abortion, Habitual; D000328:Adult; D001723:Birth Rate; D005260:Female; D005307:Fertilization in Vitro; D005820:Genetic Testing; D006801:Humans; D057194:Intention to Treat Analysis; D008423:Maternal Age; D011247:Pregnancy; D011256:Pregnancy Outcome; D018873:Pregnancy Rate; D019836:Preimplantation Diagnosis; D012189:Retrospective Studies
assisted reproduction; expectant management; preimplantation genetic screening; recurrent miscarriage; recurrent pregnancy loss