Luteal Phase Defect and Ectopic Pregnancy Dr Brendan

Luteal Phase Defect and Ectopic Pregnancy Dr Brendan Miller Endogynaecology Fellow, Flinders Medical Centre Dr Lucas Mc. Lindon Obstetrics and Gynaecology Registrar, Nambour General Hospital Dr Michael Beckmann Director of Obstetrics and Gynaecology, Mater Mothers’ Hospital AIM To present some initial findings of the Pregnancy Achieving Trial - regarding luteal phase defect, ectopic pregnancy & miscarriage. INTRODUCTION Luteal phase deficiency (LPD), while commonly observed and managed in stimulated in-vitro fertilisation cycles, is a more contentious phenomenon in natural cycles. 1 The challenge arises in the definition and diagnosis of LPD. Controversy regarding the clinical significance of LPD is due in part to the lack of a reliable test to diagnose the disorder. 2 Jones first described LPD based on temperature criteria, urinary pregnanediol studies and histological appearance of the endometrium in 1949. 3 In current practice, timing of the luteal phase from which an evaluation of its length and hormonal parameters can be made are problematic. Ovulation and thereby the length of the luteal phase can reliably and reproducibly be determined by teaching women to identify their Peak Symptom Day (PSD) of cervical mucus (the last day of any mucus discharge that is clear, stretchy, or lubricative). 4 There is an abrupt and dramatic change in the characteristic fertile pattern of pre-ovulatory mucus that is due to the effects of progesterone post-ovulation. Correlation with ultrasound and hormonal evaluation indicates that the mucus observation occurs within 2 days of ovulation. 4 Using such a fertility awareness based method, the American Academy of Fertility Care Professionals has defined a luteal phase deficiency as a deficiency in the length of the luteal phase, or a deficiency of the hormones progesterone and oestradiol that occurs during the luteal phase. METHOD Women presenting with infertility or recurrent miscarriages to the Fertility Assessment and Research Clinic of the Mater Mothers’ Hospital (Brisbane, Australia) were instructed in the Sympto-Thermal Method. This allowed for accurate documentation of ovulation and the luteal phase. Luteal phase hormone levels were collected 5, 7 and 9 days after ovulation. Women were allocated a luteal phase status using the definition below for luteal phase defect. This data is part of the recruitment phase of the Pregnancy Achieving Trials (Mater Health Services HREC no. 1618 M). Normal spontaneous cycle Cycle with a LPD Normal progesterone profile LPD definition RESULTS By the definition above , a luteal phase deficiency exists in 36% (100) of 279 infertile couples who presented to our clinic, in preparation for involvement in the Pregnancy Achieving Trials. Of 16 infertile women who had previously experienced both a miscarriage and an ectopic pregnancy, 75% (12) met the criteria for a luteal phase deficiency. DISCUSSION Ectopic pregnancy is known to be associated with infectious history, smoking, age, previous spontaneous miscarriage, history of infertility, previous use of an intrauterine device and prior history of medical termination of pregnancy (mifepristone + misoprostol). 5 Previous research has suggested an association between luteal phase defect (LPD) and ectopic pregnancy in subfertile couples. 6 All stimulated cycles of in-vitro fertilisation have abnormal luteal phases. 7 There exists a high rate of ectopic pregnancy among women undergoing in-vitro fertilization. 8 The high proportion of ectopic pregnancies among women who fall pregnant on progestogen-only contraceptives also suggests an hormonal association. 9 Women who are heavy smokers, another risk factor associated with ectopic pregnancy, has been shown to have lower urinary progesterone metabolite levels in the luteal phase compared with non-smokers. 10 CONCLUSION There appears to be an association between prior miscarriage, prior ectopic pregnancy and luteal phase deficiency in subfertile couples. Could luteal phase deficiency, an hormonal disorder, be useful in the definition of ectopic pregnancy risk? 1. The Practice Committee of the American Society for Reproductive Medicine. The clinical relevance of luteal phase deficiency: a committee opinion. Fertility and Sterility. 1 November 2012 (volume 98 issue 5 Pages 1112 -1117 DOI: 10. 1016/j. fertnstert. 2012. 06. 050) 2. Shivapathasundram G, Kwik M, Chapman M. Luteal phase defect: part of the infertility zeitgeist or relic from the past? Human Fertility. 2011; 14(1): 60 -63. 3. Jones GES. Some newer aspects of management of infertility. JAMA 1949; 141: 1123 -9. 4. Hilgers T. The Medical and Surgical Practice of Napro. Technology. PPVI Institute Press. 2004; pp 196 -203 and pp 425 -452. 5. Bouyer J, Coste J, Shojael T, Pouly J, Fernandez H, Gerbaud L, Job-Spira N. Risk Factors for Ectopic pregnancy: A comprehensive analysis based on a large case-control, population-based study in France. American Journal of Epidemiology. 2003: 157: 185 -194. 6. Guillaume AJ, Benjamin F, Sicuranza B, Deutsch S, Spitzer M. Luteal phase defects and ectopic pregnancy. Fertility and sterility. Jan 1995; 63(1): 30 -3. 7. Fatemi HM. The luteal phase after 3 decades of IVF: what do we know? Reprod Biomed Online. 2009; 19 Suppl 4: 4331. 8. Shaw JLV, Dey SK, Critchley HOD, Horne AW. Current knowledge of the aetiology of human tubal ectopic pregnancy. Human Reproduction Update. 2010; 16(4): 432 -444. 9. Furlong LE. Ectopic pregnancy risk when contraception fails, a review. The Journal of Reproductive Medicine. 2002; 47(11): 881 -885. 10. Windham GC, Mitchell P, Anderson M, Lasley BL. Cigarette smoking and effects on hormone function in premenopausal women. Environmental Health Perspectives. 2005; 113(10): 1285 -1290. Leading the way in gynaecological surgery