Analysis of IVF/ICSI Outcomes in Endometriosis Patients With Recurrent Implantation Failure: Influence on Cumulative Live Birth Rate
Main article: Endometriosis and Getting Pregnant
Endometriosis is believed to affect around 10% of women of childbearing age with as much as 50% estimated to be infertile.
Despite great advancements in the field of Assisted Reproductive Technology (ART), in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes in endometriosis patients remain unsatisfactory.
Successful embryo implantation is vital for ART to succeed however implantation failure and recurrent implantation failure (RIF) is an ongoing issue in ART.
A study in 2012, reported that endometriosis reduced the implantation rate of IVF leading to a significant decrease in the rates of clinical pregnancy and live birth.
This finding raised a key question among health professionals, can IVF/ICSI solve the infertility-related problems of endometriosis or should endometriosis be treated before IVF/ICSI.
At the same time, what role endometriosis is having in RIF is not clearly known. Studies to date have mostly examined endometriosis and RIF as independent issues creating a lack of evidence to counsel affected patients.
To examine the effect of endometriosis treatment on pregnancy outcomes in RIF patients and define the most suitable treatment option in regards to pregnancy rates.
An ambispective cohort study was conducted using the ART database (July 2008 to August 2018), at the First Affiliated Hospital of Nanjing Medical University.
The following patients were excluded from the study:
- Patients using donated oocyte/s
- Patients undergoing in vitro maturation (IVM)
- Patients who underwent fertility preservation cycles, due to chemotherapy or cancer
- Patients with missing information
After applying the elimination criteria, 330 patients (1043 cycles) with endometriosis and RIF were selected for the study and categorised into 3 groups:
- Group A (untreated), included 141 RIF patients (374 cycles) who did not receive any treatment for endometriosis
- Group B (early-treatment), included 94 patients (326 cycles) who received endometriois treatment before the diagnosis of RIF but continued to suffer from RIF
- Group C (late-treatment), included 95 patients (343 cycles) who received endometriosis treatment after the diagnosis of RIF.
Endometriosis was confirmed by either transvaginal ultrasound (endometrioma), surgery or clinical checklist (94% accuracy) while RIF was defined as the failure to achieve clinical pregnancy following 3 or more fresh or frozen embryo transfer cycles, using at least 2 high-quality blastocysts or 4 high-quality embryos in total.
Treatment of endometriosis for Group B and C patients was carried out via laparoscopic surgery and/or at least 2 doses of gonadotropin-releasing hormone agonist (GnRh-a).
The main outcomes analysed were clinical pregnancy rate, live birth rate and cumulative birth rate. Moreover, fertilization rate, available embryo rate and high-quality embryo rate were also compared.
Initial analysis of baseline characteristics revealed no statistically significant difference with respect to age, AMH (Anti-Mullerian hormone), basic follicle-stimulating hormone (bFSH) and antral follicle count (AFC) among the 3 groups.
Similarly, analysis of main outcomes revealed the differences in both the clinical pregnancy rate and the live birth rate (per number of transfer cycles), between the 3 groups, was not statistically significant although a gradual increase in the latter was noted.
|Adenomyosis rate (%)||1.1||12.1||7.6|
|Ovarian surgery (%)||13.1||31.6||19.9|
|Mild and suspected endometriosis (%)||89.6||69.5||80.7|
|Clinical pregnancy rate (%)||30.1||29.9||32.8|
|Live birth rate (%)||21.3||23.6||25.7|
|Cumulative live birth rate (%)|
|– 1st cycle||18.4||26.6||30.5|
|– 2nd cycle||24.1||34.0||43.2|
|– 3rd cycle||25.5||40.4||44.2|
|– 4th cycle||27.7||41.5||45.3|
|– 5th cycle||27.7||42.6||45.3|
|Total Cumulative live birth rate (%)||27.7||43.6||46.3|
On the other hand, calculation of cumulative live birth rates (per patient), up to the 5th cycle, demonstrated a significant improvement in the treated groups (Group B: 43.6% and Group C: 46.3%) versus the untreated group (Group A: 27.7%), even with significantly higher adenomyosis and ovarian surgery rates among treated women.
Analysis of laboratory outcomes also revealed a statistically significant difference among fertilization rates, with the early-treatment group having better results (64.4%) compared to both, the late-treatment group (60.3%), and untreated group (46.2%).
Available embryo rate for transfer was also higher (90.3%) in the early-treatment group, but similar for the other 2 groups, 85.2% (untreated) and 85.5% (late-treatment).
Although both treatment groups had much higher high-quality embryo rates, 76.5% (early-treatment) and 70.8% (late-treatment), than the untreated group (64.5%).
Advanced statistical (Kaplan-Meier curve) analysis showed that the time taken to achieve a live birth was 23.1 months for the untreated group, while it was around 18.5 months and 14.2 months for the early treatment and late treatment groups respectively.
The difference in outcomes among the 2 treatment groups may be explained in part by the recurrence of endometriosis and or the higher proportion of women with unexplained infertility among the early-treatment group.
SUMMARY: SHOULD ENDOMETRIOSIS BE TREATED BEFORE IVF
In this study, women who treated endometriosis before in vitro fertilization (IVF) had significantly improved cumulative live birth rates (46.3 vs. 27.7 %) and reduced time to live birth (14.2 vs. 23.1 months) compared to (untreated) women with endometriosis who tried IVF first.
- The time from endometriosis treatment to ovarian stimulation for IVF/ICSI was different between Group B (early-treatment) and Group C (late-treatment) meaning different duration of GnRH-a use which can impact the number and quality of oocytes retrieved.
- The potential effect of different IVF treatment protocols was not examined in this study.
This study was funded by the National Key Research and Development Program of China, the National Natural Science Foundation of China, and a Maternal and Child Health of Jiangsu Province China program.
A condition where cells from the uterus lining grow into the muscle of the uterus.
Retrospective and prospective.
Anti-Mullerian Hormone (AMH)
A hormone produced by the small follicles in a woman’s ovaries, commonly used as a marker of oocyte quantity.
Antral Follicle Count (AFC)
A test performed via ultrasound to evaluate a female’s ovarian reserve.
A fertilised embryo that has developed an inner cell mass and outer layer (trophoblast) some time from day 4 onwards.
An increasing total after successive additions.
The presence of endometrial tissue on the ovary.
Gonadotropin-Releasing Hormone agonist (GnRh-a)
An agent which suppresses the pituitary production of gonadotrophins (LH, FSH) vital for the production of estrogen and progesterone.
A minimally invasive surgical technique used to access the interior of the abdomen or pelvis.
Unfertilised immature / mature egg.
Boucret L, et al. (2020). Endometriosis Lowers the Cumulative Live Birth Rates in IVF by Decreasing the Number of Embryos But Not Their Quality. https://doi.org/10.3390/jcm9082478
Coccia M E, et al. (2011). Impact of Endometriosis on In Vitro Fertilization and Embryo Transfer Cycles in Young Women: A Stage-Dependent Interference. https://doi.org/10.1111/j.1600-0412.2011.01247.x
Al-Azemi M, et al. (2000). Ovarian Response to Repeated Controlled Stimulation in In-Vitro Fertilization Cycles in Patients With Ovarian Endometriosis. https://doi.org/10.1093/humrep/15.1.72
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