1. ASSISTED REPRODUCTION TECHNIQUESBY
DR SUHAILA FADHIL AL-SHAIKH
CABMS(OG), FICMS(OG)
Assist prof. / OB & GYNE DEPT / COLLEGE
OF MEDICINE / BABYLON UNIVERSITY

3. Assisted conception
Assisted conception is the facilitation of natural conception by some form of scientific intervention.

4. Assisted Reproductive Technologies (ART)
Assisted Reproductive Technologies are procedures that either place sperm inside the women reproductive tract or employ techniques that retrieve eggs from the ovary and reimplant the embryos . Fertilization may occur either in the lab. or in the uterus.

5. These techniques include the following
Artificial Inseminations (AIs).
Conventional IVF.
Gamete intra fallopian transfers (GIFT).
Zygote intra fallopian transfers (ZIFT).
Pronucleated oocytes transfer (PROST).
Tubal embryo transfers (TET).
Micromanipulation; this include :
Partial Zona Dissection (PZD).
Sub Zonal Insemination (SUZI).
Intra-Cytoplasmic Sperm Injection (ICSI).

6. ART PGD: Preimplantation genetic diagnosis
PGS: Preimplantation genetic screening
MESA: Microepididymal sperm aspiration
PESA: Percutaneous epididymal sperm
aspiration
TESE: Testicular sperm extraction
GIFT: Gamete intrafallopian transfer

7. Assisted conception
John Hunter, in London in was the 1st doctor who tried the ART: When the husband, in this infertile couple , had hypospadias and artificial insemination of ejaculated sperm was performed on the wife.
This resulted in a successful pregnancy and subsequent birth.

8. Investigations before starting ART
Ovarian reserve testing this includes:
CD3 FSH, antimullarian hormone level, and inhibin A & B, AFC and ovarian volume by TVS.

9. IUI
ICSI
IVF

10. Artificial Inseminations (AI):
Artificial inseminations are term that cover arranges of techniques of placing the sperm in the female genital tract .These techniques may be:
Intrauterine insemination (IUI).
Intracervical insemination (ICI).
Intravaginal insemination (IVI).
Intrafallopian insemination or Intratubal insemination (ITI).
Intraperitoneal insemination (IPI).
Intrafollicular insemination (IFI).

11. Conventional IVF
Conventional IVF treatment has grown dramatically and is now practiced in many clinics around the world.

12. in 1978 Louise Brown was born

13. The primary indications for IVF
Absence of a functional Fallopian tubes, poor sperm quality, and refractory anovulation)
inoperable tubal blockage was the primary indication for the first patient treated by IVF.
Oligoasthenozoospermia, teratozoospermia, or any combination of these, IVF offers the best chance of achieving fertilization.
Endometriosis.
Unexplained infertility.
Multiple factors, female, one or more female causes or female and male factors infertility .

15. Pioneer Pro-Pump Single Vacuum

16. Conventional IVF Atypical IVF procedure is as follows:
1. The gynecologist first induces superovulation
2. Ovum retreival either by transvaginal ultrasound guided large gauge needle (16-17) which is done usually after hours after HCG administration.

17. 3. Semen preparation by one of the in vitro preparation techniques, usually two hours before oocyte recovery.
4. Gamete loading, where active sperms added to oocyte in a Petri dish and kept in incubator and monitor microscopically for signs of fertilization and cell division (cleavage), usually fertilization occurs hours later.

18. 5. Embryo transfer, the embryo (cell number 2, 4, 8, 16) are reimplanted into the uterus this is done transcervically using special catheter . The probability of successful pregnancy is enhanced by inserting up to 3 embryos.
6. The patient remains in the supine position for 1hr-several hours.
7. Luteal phase support by progesterone administration. It takes two weeks to determine if the process is successful, by doing serum hCG 14 days after the oocyte recovery.

19. Controlled ovarian stimulation (COS)
Protocols of multiple follicles growth:
Using the (FSH) either pure or mixed with LH for COS , there are many protocols
1- Long protocol
2- Short
3- ualtra short
*Dose monitored until (1) 1-2 leading follicle.
(2) 17-18m size.
**GnRH-a :for pituitary down regulation (to prevent premature LH surge).

20. Ovum retreival
-By 1970, Stepto and Edwards had developed a laparoscopic method for aspirating oocytes from Graafian follicle a major development was the change from laparoscopic to transvaginal ultrasound guided aspiration.

21. Transvaginal retrieval with vaginal transducer
The puncture is carried out through the vaginal forncies with an empty bladder Advantages: -very short puncture distance -untouched urinary bladder -no skin wound

22. T/V Ovum retrieval

23. Embryo Transfer (ET)
The ultimate goal of a successful ET ( usually 2-3 embryos), to deliver the embryos atraumatically near the uterine fundus without pain , trauma to the endometrium or embryos , and the absence of the uterine contraction

24. ET
the success of embryo implantation influenced by various factors including
- The age of patient.
- Quality of embryos.
- Receptivity of the
uterus .

26. NON CONVENTIONAL IVF Blastocyst transfer
Zona Hatching or Assisted Hatching
Micromanipulation of gametes: Intracytoplasmic sperm injection (ICSI), Partial Zona Dissection (PZD),
Sub Zonal Insemination (SUZI).

27. ICSI
It is an modalities of IVF, to allow as single sperm cell to be injected directly into an egg. When the sperm count is extremely low or there is poor semen quality or if the sperm must be taken from the epididymus or testicle, this technique can be very useful .It has broadened the use of IVF.

28. ICSI
The ICSI procedure is also suggested when oocytes are to be considered for preimplantation genetic diagnosis (PGD), .
It has been found that there is no difference in birth defect rates between ICSI and standard IVF procedures. Immature sperms (spermatids) are now being used in ICSI as well and the long term genetic implication of this remain unknown .

30. Techniques used in AR and their outcome

31. Classification of OHSS

32. Risk factors for OHSS

33. When there is reduced ovarian reserve

34. Endometriosis: -In ART , facing relatively poor out come.
-IVF – program data suggest:
1-Diminished ovarian reserve.
2-Poor oocyte quality.
3-Poor embryo quality.
4-Impaired implantation.
5-Peritoneal cytokines shown to be toxic to
sperm

35. DREAM

36. CLOMIFENE CITRATE Recommended dosage:
Typically 100 mg administered between cycle days 3 and 7. Limit the duration of
treatment to 3–4 months. Instruct couples to use an ovulation predictor kit or
have intercourse every other day between cycle days 10 and 18.
Pregnancy rate
The pregnancy rate is 6% per cycle.

37. Options for the CC failures
1. Increasing CC doses up to 250 mg per day. In clinical experience, doses beyond 150 mg per day are rarely effective.
2. Metformin – of those patients who fail to respond to CC alone, if they are pretreated with metformin 500 mg t.i.d. for 4–6 weeks prior to another course of CC, 90% will ovulate.
3. Dexamethasone
4. Injectable gonadotropins.

38. Caution
These patients are at significant risk of a multiple pregnancy – the goal of
the stimulation is 1–2 follicles. If more than 2 follicles ≥ 16 mm or if several
secondary follicles are present > 12 mm, consideration should be given to canceling the cycle

39. Hypothalamic dysfunction
Since these patients are deficient in FSH and LH, both of these hormones need to be replaced. Therefore, human menopausal gonadotropins (HMG) (Menopur®,Repronex®) must be administered or pure LH (Luveris®) can be added to pure FSH. It is important that low doses (75 IU) be administered initially and one is cautious in raising the dose.
1. Human choronic gonadotropin (HMG) 75 IU × 5–7 days then check estradiol (E2) and ultrasound (US).
(a) If E2 < 50 increase by 37.5 IU × 3 days then repeat the E2/US. Increase HMG by no more than ½ amps every 3–4 days.
(b) If E2 > 50 continue the same dose and repeat monitoring every 2–3 days.
2. Administer hCG when lead follicle is ≥16 mm.

40. Polycystic ovarian disease:
These patients are deficient in FSH and have elevated circulating levels of LH.
Therefore, only FSH containing medications (Gonal F®, Bravelle®, Follistim®) are
needed to correct the ovulatory dysfunction.
1. FSH 75 IU × 5 days then check E2 and ultrasound.
(a) If E2 < 50 increase by 37.5 IU × 3 days then repeat the E2/US. Increase HMG by no more than ½ amp every 3–4 days.
(b) If E2 > 50 continue the same dose and repeat monitoring every 2–3 days.
2. Administer hCG when lead follicle is ≥ 16 mm.

41. Caution:
These patients are at risk of a multiple pregnancy and OHSS – the goal of the stimulation is 1–2 follicles. However, the success rate in the PCO population is lower that in those patients with hypothalamic dysfunction. If more than 3–4 follicles ≥ 16 m develop on ultrasound examination, or if several secondary follicles > 12 mm are present, then consideration should be given to canceling the cycle.

42. Dexamethasone
Dexamethasone can be considered for the anovulatory woman who fails to respond to increasing doses of CC or who is noted to have an elevated dehydro-epiandrostenedione (DHEAS) level.
An elevated DHEAS level may suggest an attenuated adrenal enzyme deficiency.
Other causes include an adrenal tumor and Cushing’s syndrome.

43. The administration of dexamethasone will decrease the adrenal androgen contribution to the pool of androgens. In some cases, this will be enough to improve the response to CC. Dexamethasone should be administered at night at a dose of 0.5 mg. One month after starting the dexamethasone, a morning cortisol level should be checked.
A cortisol level less than 3 μg/dl suggests significant depression of cortisol synthesis by the adrenal gland, which could interfere with a stress response by the adrenal gland.
In this circumstance, the dose or frequency of administration should be decreased. The use of dexamethasone should be avoided during pregnancy.

44. LETROZOLE
Letrozole is an aromatase inhibitor. Its trade name is Femara® and it is approved by the FDA for adjunctive of breast cancer but not approved for fertility treatment. The use of letrozole in the infertile population was the topic of a recent review By inhibiting the aromatase enzyme, letrozole causes a drop in estrogen levels which results in release of FSH by the pituitary gland.
Unlike CC, letrozole does not have detrimental effects on the cervical mucus and endometrial lining.
Letrozole is available in 2.5 mg tablets and it is taken once a day.

45. is 2.5 mg per day, and can be increased up to 7.5 mg a day for 5 days.
The standard dose
is 2.5 mg per day, and can be increased up to 7.5 mg a day for 5 days.
Side-effects
are nausea, dizziness, hot flashes, and headache.
Risks
include twins, 5–10%; or triplets
Ovarian hyperstimulation syndrome is theoretically possible.

46. IMPORTANT NOTE
A recent study reported an increased incidence of locomotor and cardiac malformations in babies conceived using letrozole. Until additional published data are available this medication should be used with caution and the patient needs to be advised of the potential increased risk of malformations.
All patients prior to taking this medication should have a serum pregnancy test.