Time to resolution of tubal ectopic pregnancy following methotrexate treatment: A retrospective cohort study.

OBJECTIVE: To determine the time to resolution of tubal ectopic pregnancy after methotrexate treatment. METHODS: A 14-year retrospective cohort study was performed from 2004-2018 and assessed 216 women treated with single-dose methotrexate for tubal ectopic pregnancy. Women were treated using a single-dose protocol of intramuscular methotrexate (50mg/m2) for confirmed tubal ectopic pregnancy on ultrasound. Ectopic pregnancies were included if the ectopic pregnancy mass was <35mm, no evidence of rupture and no embryonic cardiac activity. Serum hCG was measured on day 1, 4 and 7 of treatment and then at standard weekly intervals until resolution. Where there was not a ≥15% decline in hCG from day 4 and day 7, a second dose of methotrexate was administered. The primary outcome was time to resolution (days), with serum hCG <5 IU/L considered resolved. The secondary outcome was need for rescue surgery. RESULTS: Among women who did not proceed to surgery, the median time to resolution was 22 days (IQR 14,34). Time to resolution and need for rescue surgery increased with baseline hCG. When hCG was <1000 IU/L, the median was 20 days (IQR 13,29) but 34.5 days (IQR 22,48) with hCG >2000 IU/L. Early hCG trends were predictive of time to resolution and likelihood of rescue surgery; a hCG rise of >1000 IU/L between Days 1-4 increased time to resolution to 61 days (IQR 35,80) and an odds ratio of rescue surgery of 28.6 (95% C.I. 5.3,155.4). CONCLUSION: The median time to resolution for ectopic pregnancies treated with methotrexate is 22 days and associated with baseline hCG levels. The predictive value of baseline hCG may be useful in clinical decision making and counselling women considering methotrexate for ectopic pregnancy.

Gonadotropin-Releasing Hormone-Agonist Triggering and a Freeze-All Approach: The Final Step in Eliminating Ovarian Hyperstimulation Syndrome?

IMPORTANCE: In vitro fertilization (IVF) has evolved dramatically in recent decades; however, clinical practices have been slow to adopt these advancements, particularly regarding final oocyte maturation and the timing of embryo transfer. Concerns still exist over the ability of gonadotropin-releasing hormone (GnRH) agonists and elective embryo cryopreservation to reduce the risk of ovarian hyperstimulation syndrome (OHSS) without compromising pregnancy outcomes. OBJECTIVE: This review investigates IVF outcomes associated with GnRH-agonist triggering and elective embryo cryopreservation. The safety and efficacy of GnRH-agonist triggering are compared with conventional human chorionic gonadotropin triggering, and frozen embryo transfers are weighed against fresh transfers. EVIDENCE ACQUISITION: A literature search was conducted using OVID (MEDLINE) and PubMed databases. The search strategy included keywords such as "ovarian hyperstimulation syndrome or OHSS," "GnRH-agonist triggering," "cryopreservation or freeze-all," and "IVF outcomes." A total of 214 articles were considered for review. RESULTS: Gonadotropin-releasing hormone agonist triggering reduces OHSS incidence without compromising oocyte retrieval and fertilization rates in donor and autologous cycles. However, GnRH-agonist triggering causes a luteal phase deficiency in autologous cycles, deleteriously compromising pregnancy rates. Elective embryo cryopreservation overcomes this deficiency, reducing the risk of OHSS and may improve neonatal and obstetric outcomes. CONCLUSIONS: Gonadotropin-releasing hormone agonist triggering should be considered in all donor cycles. It should also be selectively considered in autologous cycles in combination with elective cryopreservation of all viable embryos.