Brief Review of In-vitro Fertilization

Prepared by:Prabhat KC

Raksha Sharma

Contents

• Introduction• Indications• Patient selection• Advantage/ Disadvantage• Procedure

Introduction

• Is a treatment for infertility• Oocytes are fertilized by a sperm in a laboratory dish• One or more of the fertilized eggs are then transferred into woman’s

uterus , where it is hoped that they will implant and produce pregnancy• IVF cycle occur over 2 weeks time interval

Indications• Tubal disease• Unexplained infertility• Endometriosis• Male factor infertility• Failed ovulation induction• Ovarian failure• Normal ovaries but no functional uterus (Mullerian agenesis)• Women with genetic risk

Patient Selection

• Age <35 years• Presence of ovarian reserve• Husband—normal seminogram• Couple screened negative for HIV and hepatitis• Normal uterine cavity as evaluated by hysteroscopy/

sonohysterography

Disadvantages• High cost• Potential risk from fertility medications and invasive procedures• Increased multiple gestation• Pregnancy complications• Preterm birth, ectopic pregnancy

Above all this, its success rate is very high!!

Procedure• Counselling about procedure, risk and benefit• Prepare patient; history, examination and investigation• Down regulation of pituitary — GnRH agonist• Controlled ovarian hyperstimulation• Monitoring of follicular growth• Oocyte retrieval• Insemination in-vitro• Transfer of gametes or embryo• Luteal support with progesterone

IVF cycle; Ten teachers

Down Regulation of Pituitary Gland

• GnRH analogue down regulation of pituitary prevent premature LH surge• prevention of LH surge during stimulation would prevent in follicular

rupture of prior to egg retrieval • Allows significantly higher number of oocyte retrieval, improve

endometrial receptivity and pregnancy rates• Given by daily injection or nasal spray

Controlled Ovarian Hyper-stimulation• Started once pituitary down regulation achieved• Serum E2<40 pg/ml and no ovarian follicles seen >10 mm on TVS

• Regimens• Colmiphene citrate (CC)• CC + human menopausal gonadotrophin( hMG)• CC + pure FSH• CC + recombinant FSH• hMG• GnRH analogues + hMG or pure FSH

Monitoring of follicular Growth• Cervical mucus study• Sonographic measurement of follicles• Serum estradiol estimation

• When >= 2 follicles 17-18 mm in diameter and serum E2 level> 250 pg/ml/follicle5,000-10,000 IU of IM hCG given

• hCG induces oocyte maturation

On 8th day of treatment cycle

Oocyte Retrieval

• Transvaginal under ultrasound is done • Oocyte retrieved 36 hours after the hCG given but before ovulation• After recovery the oocytes are maintained in culture in vitro for 4-6

hours

Insemination; In-vitro• Sperm

• prepared by the wash and swim-up or density gradient centrifugation technique

• Approx. 50,000 to 100,000 capacitated sperms • placed in culture media containing oocyte within 4-6 hours of retrieval

• After 16-18 hours• examined for presence of pronuclei confirms fertilisation

• Zygotes returned to incubator allow cleavage to 2-4 cell stage when ready transfer to uterus• Sperm density and motility are two most important criteria for successful

IVF

Embryo Transfer

• Carried out 48-50 hours after oocyte recovery, ie 46-48 hours after insemination • The fertilized ova (not >3) at the 6-8 blastomere stage • to minimize multiple pregnancy

• Placed into the uterine cavity close to the fundus• Through a fine flexible soft embryo transfer catheter transcervically

No. of embryo to transfer

• Young age( < 35 years)• Only one or two embryo• If multiple attempts of IVF are failed then more than one or two embryo

• > 40 years age• More embryos( often 5) • Older women who received eggs from youngers donors have rate of

implantation similar to that of younger women and are advised to transfer one or two embryo

Luteal Phase Support

• Maintained with progesterone• Started on the day after oocyte retrieval• hCG given in supplemental dose (1500-2500 IU)• Post transfer, patient receives • Progesterone; for 14 days

• Micronised progesterone, 200 mg, thrice daily per oral OR as a vaginal suppository OR • Progesterone in oil injection 50 mg IM

Complications

Short term• Miscarriage• Multiple pregnancy• Ectopic pregnancy• Low birth weight baby• Premature baby• Pain, bleeding, trauma, infection

during oocyte retrieval

Long term• Premature ovarian failure• Ovarian cancer due to hyper-

stimulation• Breast cancer

Testing of Pregnancy• Approx. two weeks after embryo transfer blood or urine for hcg

signifies pregnancy• If Blood hcg < 5IU/L , women is not pregnant• If hcg> 10 IU/L , repeat after 48 hrs• hcg level doubled every 48 hrs during 21 days after embryo transfer.• If not , pregnancy not progressed normally• USG:

• If hcg levels increases as expected pelvic USG is done 304 wks after the transfer.• To see gestational sac inside uterus

References

• Shaw’s Textbook of Gynecology, 15th edition.• Upto Date

Thank You