SO+IUI After Operative Laparoscopy in Patients With Advanced Stage Endometriosis

This is a prospective randomized control, crossover trial that will be performed examining
fertility outcomes in patients after ablative and/or excisional operative laparoscopy at the
Cleveland Clinic for infertility due to advanced stage (III/IV) endometriosis. Patients will
be randomized to either receive immediate (three months) clomiphene citrate at 100mg daily
for SO+IUI or expectant management with timed intercourse for three months. After 3 months,
patients will cross over to the other treatment arm, receiving either three additional months
of SO+IUI or three months of expectant management. Monthly fecundity rates and additional
outcomes will be monitored.

The study population will include women 18 to 35 years old with a diagnosis of infertility,
defined as actively attempting to achieve pregnancy for >12 months of unprotected
intercourse, prior to undergoing operative laparoscopy to treat endometriosis. Using the ASRM
classification criteria, all patients included will have a diagnosis of stage III or IV
endometriosis from a surgery performed within the Cleveland Clinic Foundation. Patients who
present with idiopathic infertility who are found to have advanced stage endometriosis on
diagnostic laparoscopy will be included as long as ablation and/or excision was performed on
all visible endometriosis and adhesions. All patients must have at least one patent fallopian
tube, assessed by hysterosalpingogram, hysteroscopy, or at the time of laparoscopy via
chromopertubation. Patients with additional conditions affecting fertility will be included
given the factors are classified as mild. This includes uterine leiomyoma(s) with a normal
uterine cavity, polycystic ovarian syndrome, and mild male factor infertility (<15 million
but >10 million motile sperm per ejaculate before washing). Patients who pursue IVF after
expectant management or SO+IUI will be considered as having a negative pregnancy outcome
during their participation in the study.

Exclusion criteria include patients with additional causes for infertility such as male
factor (<15 million motile sperm per ejaculate), ovulatory dysfunction, polycystic ovarian
syndrome, age >35 years, and septate uterus. Patients who have had hormonal therapy in the
three months prior to surgery will also be excluded, as this can impact the staging of
disease. Patients will also be excluded from the study if they have previously undergone
treatments for infertility, such as ovulation induction, IUI and/or IVF.

Potential study participants will be identified by members of the Fertility Center within the
Cleveland Clinic Women's Health Institute, as well as by chart review performed by the
research coordinator. Women who present to the Cleveland Clinic for evaluation of infertility
and are scheduled to undergo surgical intervention will be evaluated for participation in the
study. A thorough chart review will be performed to ensure that all inclusion criteria for
the study are met. At this time, a copy of the informed consent will be mailed to any patient
who meets the study criteria. The primary investigator will call the patient ~1week after the
consent document was sent to discuss the study with the patient. For patients with known
stage III or IV endometriosis, contact for enrollment into the study will occur after their
preoperative visit. Patients with idiopathic infertility who are found to have stage III or
IV endometriosis at the time of laparoscopy will be contacted in a similar fashion in the
postoperative period. During the phone conversation with the primary investigator, the
informed consent process will be described to the patient. Preferentially, patients will
schedule a time to meet with the research coordinator to sign the informed consent document
at main campus. A one-time parking validation will be provided for these patients. In an
effort to accommodate individuals who are unable to travel to main campus to sign the
informed consent, the patient will be permitted to sign the document and return it to main
campus by mail. The primary investigator will then sign the document and a copy will be
mailed back to the patient. The method by which the patient signed the consent, as well as
the time line throughout the consent process will be documented in the patient's Epic chart.
After informed consent, patients will be randomly assigned to the initial treatment group in
the postoperative period. Patients initially assigned to SO+IUI will have a quantitative hCG
level drawn after three weeks after IUI. Patients initially assigned to expectant management
will be contacted after 3 months to evaluate whether or not spontaneous pregnancy was
achieved. As this is a crossover study, patients who do not achieve pregnancy during their
initial treatment arm, cross over will occur and patients will undergo 3 months of the
remaining treatment arm.

Inclusion Criteria:

- Using the ASRM classification criteria, all patients included will have a diagnosis of
stage III or IV endometriosis from a surgery performed within the Cleveland Clinic
Foundation.

- Patients who present with idiopathic infertility who are found to have advanced stage
endometriosis on diagnostic laparoscopy will be included as long as ablation and/or
excision was performed on all visible endometriosis and adhesions.

- All patients must have at least one patent fallopian tube, assessed by
hysterosalpingogram, hysteroscopy, or at the time of laparoscopy via
chromopertubation.

- Patients with additional conditions affecting fertility will be included given the
factors are classified as mild. This includes uterine leiomyoma(s) with a normal
uterine cavity, polycystic ovarian syndrome, and mild male factor infertility (<15
million but >10 million motile sperm per ejaculate before washing).

Exclusion Criteria:

- Exclusion criteria include patients with additional causes for infertility such as
male factor (<15 million motile sperm per ejaculate), ovulatory dysfunction,
polycystic ovarian syndrome, age >35 years, and septate uterus.

- Patients who have had hormonal therapy in the three months prior to surgery will also
be excluded, as this can impact the staging of disease.

- Patients will also be excluded from the study if they have previously undergone
treatments for infertility, such as ovulation induction, IUI and/or IVF.