Preimplantation Genetic Testing (PGT) alongside assisted conception may be of use.

Introduction 

There are currently no studies evaluating the benefit of IVF/ICSI  in couples with RPL. However, Preimplantation Genetic Testing (PGT) alongside assisted conception may be of use. There are essentially two key types:  

  1. For couples with no known karyotype issue: Preimplantation genetic testing for aneuploidy (PGT-A) involves couples undergoing an ART cycle to create embryos which are biopsied and screened for aneuploidy prior to embryo transfer. A systematic review looking at PGS (PGT-A) for those couples with no known chromosomal abnormality concluded that there is no improvement in live birth rate with PGT (PGT-A)1. However, by reducing transfer of aneuploidy embryos it does appear to reduce the rate of miscarriage. In couples where there has been a long interval since their last pregnancy, PGT-A can be considered if ART is offered as a treatment for infertility.
  2. For couples with a karyotype issue: In couples where a balanced translocation has been identified, Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR) involves the biopsy of embryos to identify those that are unaffected by the translocation. Couples may also wish to incorporate PGT-A as above.  Cases for PGT-SR should be referred by the regional genetics service to specialised PGT providers and may be entitled to NHS funding if they have no healthy children.

Bullet point guidance 

  • At present, there is no evidence to justify IVF alone as a treatment option in couples with unexplained recurrent pregnancy loss.
  • The limited evidence for preimplantation genetic testing of aneuploidy (PGT-A) in couples with RPL shows no clear benefit (in terms of live birth rate) of treatment, though miscarriage is reduced.
  • In couples with known chromosomal translocations / karyotypic issues then preimplantation genetic testing for structural rearrangements (PGT-SR) should routinely be offered.
  • In women with a history of RPL who have not conceived naturally for twelve months, baseline fertility investigations should be performed and the woman should be referred to the local fertility services, where couples can be counselled regarding PGT. These investigations include:
  • Seminal fluid analysis.
  • Ovarian reserve testing, using total antral follicle count, serum anti-müllerian hormone (AMH) levels or early follicular phase FSH levels.1
  • Confirmation of ovulation, by measuring serum progesterone in the mid-luteal phase of the menstrual cycle (e.g., day 21 of a 28-day cycle).1
  • Women with irregular menstrual cycles should be offered a random FSH, LH, prolactin and thyroid-stimulating hormone.1 
  • In the absence of pelvic comorbidities (g. pelvic inflammatory disease, previous ectopic pregnancy or endometriosis), tubal patency should be tested using hysterosalpingography (HSG) or hysterosalpingo-contrast-sonography (HyCoSy). Women with pelvic comorbidities should instead be offered laparoscopy and dye test.1

References 

  1. Musters AM, Repping S, Korevaar JC, Mastenbroek S, Limpens J, van der Veen F, Goddijn Pregnancy outcome after preimplantation genetic screening or natural conception in couples with unexplained recurrent miscarriage: a systematic review of the best available evidence. Fertility and Sterility 2011;95: 2153-2157, 2157.e2151-2153.
  2. The ESHRE Guideline Group on RPL, Ruth Bender Atik, Ole Bjarne Christiansen, Janine Elson, Astrid Marie Kolte, Sheena Lewis, Saskia Middeldorp, Willianne Nelen, Braulio Peramo, Siobhan Quenby, Nathalie Vermeulen, Mariëtte Goddijn, ESHRE guideline: recurrent pregnancy loss, Human Reproduction Open, Volume 2018, Issue 2, 2018, hoy004, https://doi.org/10.1093/hropen/hoy004