2. Recurrent Pregnancy Loss

3. loss of two or more pregnancies spontaneous demise of a pregnancy before the fetus reaches viability from the time of conception until 24 weeks of gestation .
Primary RPL
secondary RPL

4. Pregnancy loss is a significant negative life event mostly focused on women, need for studies on the emotional impact of RPL on men.
Clinicians and clinics should take the psychosocial needs of couples faced with RPL

5. Risk factors and health behavior

6. occupational or environmental exposure .
INFECTION
occupational or environmental exposure .
S T RESS
Female age
Male age
SMOKING
Maternal&paternal obesity or being significantly underweight

7. Investigations in RPL

8. Genetic analysis of pregnancy tissue is not routinely recommended but it could be performed for explanatory purposes (CGH array) Parental karyotyping is not routinely recommended in couples with RPL. In case of established carrier status, couples should be advised that the long-term prognosis of a live birth is good in carriers of a structural chromosome abnormality (LBR of 71% in 2 years).

9. Treatment for RPL with genetic background PREIMPLANTATION GENETIC SCREENING P RE IMPL ANTATION GENETIC DIAGNOSIS All couples with results of an abnormal fetal or parental karyotype should receive genetic counselling. All couples with results of an abnormal fetal or parental karyotype may be informed about the possible treatment options available including their advantages and disadvantages.

10. Thrombophilia screening
Factor V Leiden mutation
Prothrombin mutation
Protein C, Protein S and Antithrombin deficiency
For women with RPL, we suggest not to screen for inherited thrombophilia unless in the context of research.

11. ACQUIRED
THROMBOPHILIA

12. ACQUIRED THROMBOPHILIA
Antiphospholipid antibodies (LA and ACA [IgG and IgM]),
β2GPI can be considered after two pregnancy losses.

13. Treatment for RPL and Thrombophilia
Folic acid and vitamins
Most studies on treatment with folic acid and vitamins have focused on RPL
women with a mutation in the MTHFR gene and/or hyperhomocysteinemia
For women who fulfill the laboratory criteria of APS and a history of two or more pregnancy losses, we suggest antepartum administration with low-dose aspirin (75 to 100 mg/day), and a prophylactic dose heparin (UFH or LMWH) starting at date of a positive pregnancy test 8

14. Immunological screening

15. anti-HY antibodies in RPL patients is not recommended in clinical practice.
HLA determination in women with RPL is not recommended in clinical practice
HLA class II determination (HLA-DRB1*15, DRB1*07 and HLA-DQB1*0501/2) could be considered in women with secondary RPL after the birth of a boy, for prognostic purposes.

16. Cytokine polymorphisms should not be tested in women with RPL.
Antinuclear antibodies (ANA) testing for explanatory purposes
. NK cell testing is not recommended in women with RPL
Anti-HLA class I or II antibodies
Celiac disease serum markers
Antisperm antibodies

17. Metabolic and endocrinologic factors

19. Vitamin D supplementation
Preconception counseling in women with RPL could include the general advice to consider prophylactic vitamin D supplementation
(4000 IU/d dose of vitamin D3) can be considered safe.
HYPER HOMOCYSTEINEMIA
(risk factor for venous thromboembolism, and adverse pregnancy outcomes
Assessment of PCOS, fasting insulin and fasting glucose is not recommended in women with RPL to improve next pregnancy prognosis

20. Ovarian reserve testing is not routinely recommended in women with RPL
Prolactin testing is not recommended in women with RPL in the absence of clinical symptoms of hyperprolactinemia (oligo/amenorrhea)
Ovarian reserve testing is not routinely recommended in women with RPL

21. Anatomical investigations

23. Treatment for uterine abnormalities in RPL A CQUIRED INTRAUTERINE ANOMALY 1 POLYP.>1CM 2 Fibroids Surgical removal of intramural fibroids is not recommended in women with RPL. There is insufficient evidence to recommend removing fibroids distorting the uterine cavity 3-Intrauterine adhesions (IUA) (Asherman’s syndrome)

24. Male factors

25. Assessing sperm DNA fragmentation in couples with RPL
In the male partner, it is suggested to assess life style factors (smoking, alcohol consumption, exercise pattern, and body weight)
Assessing sperm DNA fragmentation in couples with RPL

26. Couples with RPL should be informed smoking, alcohol consumption, obesity excessive exercise could have a negative impact on their chances of a live birth, and therefore cessation of smoking, a normal body weight, limited alcohol consumption and a normal exercise pattern is recommended Sperm selection is not recommended as a treatment in couples with RPL. Antioxidants for men have not been shown to improve the chance of a live birth in couples with RPL.

27. Assessing prognosis of a couple with RPL
Reproductive history
Sex of first born
Family history
Previous miscarriage history and age of the patient significantly affected the chances of a successful outcome, age being slightly more significant than previous number of miscarriages

28. There is insufficient evidence to recommend the use of progesterone to improve live birth rate in women with RPL
There is insufficient evidence to recommend the use of hCG to
improve live birth rate in women with RPL and luteal phase insufficiency.
There is insufficient evidence to recommend metformin supplementation in pregnancy to prevent PL in women with RPL and glucose metabolism defects.

29. Pituitary suppression before induction of ovulation in women with RPL and PCOS could be an option to reduce the risk of PL
Bromocriptine treatment is recommended in women with RPL and hyperprolactinemia to increase live birth rate.

30. Treatment for unexplained RPL

31. Lymphocyte immunization therapy should not be used as treatment for unexplained RPL as it has no significant effect and there may be serious adverse effects Treatment with allogeneic cells raises serious safety concerns and in transfusion practice great efforts are made to lymphocyte-deplete blood before used for transfusion. neonatal alloimmune thrombocytopenia production of red blood cell antibodies, which can result in erythroblastosis fetalis some risks of transferring infectious agents such as hepatitis and HIV increased long term risk of hematological malignancies.

32. Intravenous immunoglobulin (IvIg) is not recommended as a treatment of RPL
Glucocorticoids are not recommended as a treatment of unexplained RPL or RPL with selected immunological biomarkers.
There is evidence that heparin or low dose aspirin does not improve live birth rate in women with unexplained RPL.

33. There is insufficient evidence to recommended G-CSF ENDOMETRIAL SC RATCHING Intra lipid therapy should not be used for improving live birth rate in unexplained RPL, it could be harmful for the mother. of serious adverse effects has been reported after the use of intravenous lipid emulsions: acute kidney injury , cardiac arrest, acute lung injury, venous thromboembolism, fat embolism, fat overload syndrome, pancreatitis, allergic reactions increased susceptibility to infection

34. Chinese Herbal treatment
Acupuncture
Diet– antioxidants