Infertility treatment

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2 In the name of God

3 Infertility treatment

4 Treatment options The optimal treatment is one that provide an acceptable success rate, has minimal risk and is costeffective. The treatment options are: 1- Ovulation induction 2- OI + Intrauterine insemination (IUI) 3- ARTs IVF-ET ICSI GIFT- ZIFT - TET TESE PESA MESA Egg, Sperm, Embryo donation

5 Fertility medications Clomiphene citrate (Tablet 50mg) Gonadotropins (Injectable medications FSH HMG ) GnRH agonists GnRH antagonists HCG Progesterone supplements

6 Ovulation Induction Indications: Ovulatory dysfunction secondary to chronic anovulation or hypothalamic dysfunction (not for ovarian failure) Clinical strategy: CC is the initial goal, if fail to correct the ovulatory problem then gonadotropins is indicated.( Hypothalamic anovulation don t respond to CC.) Monitoring: Take CC need minimal monitoring, but gonadotropins need closer monitoring by serum E2 testing and measure follicular size by TVS.

7 Goal of treatment: is to get 1-2 mature follicles. The risks of development of too many follicles are multiple pregnancy & OHSS. Success rate: is about 6% but is variable depending on the cause of infertility. multiple pregnancy rate = 10%

8 OI + Intrauterian Insemination (IO+IUI) Indications: unexplained infertility, cervical factor, mild male factor. Clinical strategy: IUI has several steps including: ovarian stimulation sperm preparation performance of the IUI. Medication are used to increase the number of eggs that are released at the time of ovulation. in age<35y, CC 100mg/d between cycle days 3-7, monitoring ovarian response by TVS, IUI determined when LH- surge occur in age>35y, HMG is used and after follicles be matured HCG IUI. (IUI without medication for ovarian stimulation has low success rate.)

9 Semen sample is washed and prepared about the time of ovulation and then IUI is perfomed. Following IUI normal activity can be resumed. Pregnancy test is scheduled 14 day later. Success rate: after CC + IUI = 8-10% MP= 10% HMG+IUI=15-18% MP=20-25%

10 IVF and related procedures (ART) Indications: - failure of conventional treatment - Tubal damage - Sever male factor Variations: IVF-ET ICSI GIFT-ZIFT-TET MESA-PESA-TESE Egg, Sperm, Embryo donation

11 IVF IVF steps: 1) Ovarian stimulation (after pituitary down-regulation) 2) Egg retrieval 3) sperm insemination 4) Embryo transfer In all ART procedures steps 1&2 is the same, but step 3&4 are different.

12 Ovarian stimulation -*The goal of OI is to stimulate the maturity of multiple oocytes (at least 3 follicles with 15-17mm diameter) to maximize success rate of the procedure. 1- Pituitary down-regulation by GnRH-a or pituitary suppression by GnRH-ant is performed to suppress endogenous LH- surge. 2- Ovulation induction is initiated after suppression of pituitary with daily gonadotropins (HMG-FSH) 3- To follow follicular growth monitoring is done with serum E2 levels & TVS.

13 4- HCG is injected when at least 3 follicles reach a diameter of 18mm for further maturation of oocytes to allow them to become fertilized. If the response is insufficient or exaggerated (because the risk of OHSS) the cycle is cancelled.

14 Egg retrieval The egg retrieval is performed under TVS guidance by a specific needle, directed through the back wall of the vagina and directly into the ovarian follicles, under light GA. The eggs are placed in culture plate with nutrient media and then placed in the incubator. Progesterone is started the evening after the egg retrival.

15 Sperm insemination On the day of egg retrieval a sperm sample is obtained and prepared to select out the most motile sperm. About motile sperm are placed next to every egg in a culture dish and placed in the incubator. The following day the eggs are examined to determine whether fertilization has occurred. Within a few hours embryo will start to divide.

16 Embryo transfer Embryo transfer is performed usually 72 hours after the egg retrieval. Usually 2-3 embryo between 8-16 cells is transferd. Extra embryos with good quality can be frozen and stored for future use. Normal activity can be resumed after minutes of embryo transfer. Pregnancy test is conducted 11 days later. If pregnancy occur progesterone supplement must be used until GA=12w Success rate: % due to the cause of infertility. (max.= 33% in some causes of infertility)

17 Frozen embryo transfer (FET) Cryopreserved embryos can be replaced in another cycle after a spontaneous ovulation or creation of an artificial endometrium with oral E + P. Success rate : Dependent on the number & quality of embryos is between 10-20%. Advantages: ovulation induction drugs are not taken,& egg retrieval is not performed. Risk of congenital anomalies is not increased.

18 Gamete intrafallopian transfer (GIFT) Indications: 1- Altered cervical anatomy that prevents a successful uterine transfer, 2- religious reasons. Clinical strategy: Step 1&2 are the same as IVF. Sperm & 4-6 oocytes are replaced in the fallopian tube through laparoscopy. The woman must at least have one normal tube. Now there are few reasons to perform this procedure. (<2% of ART procedures are GIFT).

19 Tubal embryo transfer (TET) Indications: 1- Altered cervical anatomy, 2- GIFT is not an option (when ICSI is required). Clinical strategy : First 3 steps of IVF is done, and then 2-4 embryos are replaced in the fallopian tube through laparoscopy. The disadvantage is that 2 separate procedure are perform requiring GA including egg retrieval and laparoscopy.

20 Egg donation Indications : Poor responder women to the OI medications, Reduce ovarian reserve (POF), Whom carrier of a genetic condition. Clinical strategy : Step 1 & 2 are performed in the egg donor, then eggs are fertilized with the recipient s husband s sperm. The recipient must take E&P for create a good endometrium, and then embryos are transferred to her uterus. Success rate: is about 40%

21 Gestational carrier treatment Indications : When the woman has 1-no uterus, 2- a congenitally deformed uterus, 3- an uterus which is unable to support a pregnancy,4- has a medical condition which precludes her from successfully carrying a pregnancy. Clinical strategy : All the steps of IVF are performed but at the end of the procedure embryos are transferred into a gestational carrier.

22 Embryo donation Indications : Is performed in couples who can t have a baby from their own. Clinical strategy : Frozen embryos of a couple who don t want any more children, are replaced in the uterus of another couple who want baby but can t have one.

23 Epididymal sperm aspiration Indications : some cases of azoospermia results from vas obstruction (acquired or congenital), in cases of severely impaired sperm production. Aspiration on sperm from epididym or testis is performed. (MESA microscopic epididymal sperm aspiration, PESA percutaneous epididymal sperm aspiration, TESE testicular sperm extraction.) In all of these cases the motility of sperm is quite poor so the ICSI procedure must be performed.

24 Intracytoplasmic sperm injection (ICSI) Indications : 1- couples who have no fertilization following a previous IVF cycle, 2- severe male factor Fertilization rate = 50-70% Males with severe oligospermia (count< /cc) have greater risk for being a carrier of cystic fibrosis or having a chromosomal abnormality. There is an increased risk of sex chromosomal anomalies (4-fold increase) in male infants born following ICSI procedure.

25 Success rates of infertility treatment Factors affecting treatment outcome: 1) maternal age ( treatment is contraindicated in women>45y) 2) Ovarian reserve (even a single elevated FSH level is associated with a reduced prognosis) 3) Semen quality ( since the introduction of ICSI the severity of male factor is less important and we have only need a single viable sperm for each oocyte. Resulting embryos have the same chance of implantation. 4) Causes of infertility( impact on conservative treatments but has little impact on ARTs outcome.) 5) Duration of infertility has no impact on treatment outcome.

26 5) Pregnancy history ( Women who have had a successful pregnancy have a greater chance of success in infertility treatment. IVF treatment in women with a prior live born has a 15-20% greater chance of success.) 6) Toxic exposure ( Smoking halves the chance of achieving pregnancy-- Caffeine and alcohol reduce the chance of pregnancy.)

27 Complications of ART treatments Multiple pregnancy 1) is about 5-10% with CC 2) is about 20-25% with gonadotropins Ovarian hyperstimulation syndrome(ohss)

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