Caesarean Section and Intracytoplasmic Sperm Injection (ICSI) Outcome

Study Overview
=================
Brief Summary
-----------------
Although Caesarean section (CS) is often a necessary surgical intervention, it may also be associated with an increased risk of short- and long-term sequelae. It was thought that CS may increase the risk of female subfertility or even infertility. In assisted reproductive technology (ART) cycles, the process of implantation is believed to be the most important factor in determining pregnancy outcome. In view of conflicting results on the influence of a previous CS on outcomes of ART, this study will be conducted to investigate the impact of the mode of previous delivery on ICSI outcomes.

Detailed Description
-----------------
The use of CS has steadily increased worldwide and will continue increasing over the current decade where both unmet need and overuse are expected to coexist. The medical field now acknowledges a patient's right to actively participate in her choice of medical treatments, including the method of delivery what is known as CS on demand, a primary CS performed on the mother's request without any recognized medical or obstetric Indications that may also increase the rate of C.S. Although CS is often a necessary surgical intervention, it may also be associated with an increased risk of short- and long-term sequelae eg. infection, haemorrhage and increased risk of several obstetric complications in subsequent pregnancies, including mal-placentation, Caesarean scar pregnancies, morbidly adherent placentae and uterine rupture. It was thought that CS may increase the risk of female subfertility or even infertility. The possible reasons for this impact on fertility may be related to infections, adhesions formation, placental bed disruption or other non-medical factors (age, culture, education). Different mechanisms were hypothesized to explain the detrimental uterine environment associated with the presence of CS niche, that may lead to subfertility including accumulation of intrauterine fluid, altered immunobiology, increased inflammation, distorted contractility of the uterus caused by fibrosis or interruption of the myometrial layer at the site of the niche. In ART cycles, the process of implantation is believed to be the most important factor in determining pregnancy outcome, because the embryos are directly transferred into the uterine cavity and so the tubal factor can be excluded. To date, knowledge on the influence of a previous CS on outcomes of ART is limited with different conclusions in terms of live birth, miscarriage and implantation rates. In view of these conflicting results, more adequately powered studies are warranted. Therefore, this study will be conducted to investigate the impact of the mode of previous delivery on ICSI outcomes.

Official Title
-----------------
Effect of Prior Caesarean Delivery on ICSI Outcome

Conditions
-----------------
Female Infertility

Intervention / Treatment
-----------------
* Procedure: Frozen embryo transfer


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient age 20-35years. BMI 18- 30. Women with some indications for freeze all technique as patients with high risk for developing ovarian hyperstimulation syndrome (OHSS), patients with treatable tubal or uterine anomalies that were discovered during controlled ovarian hyperstimulation (COH) or in patients with elevated serum progesterone levels Exclusion Criteria: Severe form of endometriosis. Congenital uterine anomalies. Scarred uterus due to previous myomectomy. Women diagnosed with moderate to severe degrees of intrauterine adhesions. Women with fibroid uteri. Patients with bad quality embryos. Untreated hydrosalpinges. All fresh transfer cycles will be excluded.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group A<br>Women with history of previous one Caesarean section | Procedure: Frozen embryo transfer<br>* All women in both groups will receive oral estradiol valerate 8 mg/ day from the second day of the menstrual cycle. Endometrial thickness will be assessed by vaginal ultrasonography at the tenth day of treatment. When endometrial thickness reached ≥ 7 mm all subjects, in addition to estrogen, they will receive progesterone vaginal suppositories 400 mg twice daily and 100 mg of progesterone intramuscularly daily. Frozen thawed embryo transfer will be at day 6 of progesterone. Estrogen and progesterone will be continued until 9-10 weeks of gestation<br>|
| Group B<br>Women with history of previous normal vaginal delivery. | Procedure: Frozen embryo transfer<br>* All women in both groups will receive oral estradiol valerate 8 mg/ day from the second day of the menstrual cycle. Endometrial thickness will be assessed by vaginal ultrasonography at the tenth day of treatment. When endometrial thickness reached ≥ 7 mm all subjects, in addition to estrogen, they will receive progesterone vaginal suppositories 400 mg twice daily and 100 mg of progesterone intramuscularly daily. Frozen thawed embryo transfer will be at day 6 of progesterone. Estrogen and progesterone will be continued until 9-10 weeks of gestation<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implantation rate | The ratio between the number of gestational sacs visualized by transvaginal ultrasound and the number of transferred embryos. | 4 weeks after embryo transfer | 
| Clinical pregnancy | Determined by the visualization of a viable embryo within the uterine cavity by ultrasound 4 weeks after embryo transfer. Clinical pregnancy rate will be calculated as the number of clinical pregnancies divided by the number of embryo transfer procedures. | 4 weeks after embryo transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical pregnancy | Positive pregnancy test 11 days after embryos transfer followed by abnormally rising or subsequently declining human chorionic gonadotropin (hCG) levels along with the absence of a visualized gestational sac on a transvaginal ultrasound. The biochemical pregnancy rate is defined as the total number of biochemical pregnancies divided by the total number of positive pregnancy tests following an embryo transfer. | 11 days after embryo transfer | 
| Ongoing pregnancy | Ratio between ongoing pregnancies proceeding beyond the 20th gestational weeks to the number of embryo transfer procedures | 18 week after embryo transfer | 
| Miscarriage rate | Calculated as the total number of pregnancies that failed to progress after visualization of an intrauterine gestational sac divided by the total number of clinically recognized intrauterine pregnancies. | 18 week after embryo transfer |