What are the differential diagnoses for infertility in a 30-year-old female who stopped using Nexplanon (etonogestrel) after almost ten years?

Differential Diagnoses for Post-Nexplanon Infertility

The primary differential diagnoses include ovulatory dysfunction (particularly if she had irregular cycles before Nexplanon), tubal factor infertility, male factor infertility, diminished ovarian reserve (especially given her age approaching or in her 30s), uterine pathology, and cervical factors—though Nexplanon itself does not cause permanent infertility. 1, 2

Key Clinical Context

Nexplanon does not impair future fertility. Fertility returns rapidly after removal, with cumulative conception rates of 25% at 1 month, 49% at 3 months, 73% at 6 months, and 86% at 12 months in women attempting pregnancy post-removal 2. Nearly all women (except those with male factor infertility) conceived within 2 years 2. This means the infertility is unrelated to her contraceptive history.

Primary Differential Diagnoses

1. Ovulatory Dysfunction 3

• Most common cause of female infertility
• Critical detail: Did she have regular menstrual cycles before starting Nexplanon 10 years ago? Many women start hormonal contraception for irregular cycles without realizing they had underlying ovulatory issues 3
• Nexplanon commonly causes amenorrhea (22% of users) or irregular bleeding (34% with infrequent spotting) during use, which masks any underlying ovulatory problems 3
• Assess for PCOS, thyroid dysfunction, hyperprolactinemia, hypothalamic amenorrhea 3

2. Male Factor Infertility 2

• Accounts for approximately 30-40% of infertility cases
• Must obtain semen analysis early in evaluation—this is often overlooked and delays diagnosis 2
• In the fertility study of post-Norplant users, the only women who remained non-pregnant at 2 years had documented male factor infertility 2

3. Tubal Factor Infertility 3

• History of sexually transmitted infections (particularly chlamydia or gonorrhea) over the 10-year period 3
• Prior pelvic inflammatory disease, ectopic pregnancy, or abdominal/pelvic surgery 3
• Note: Nexplanon does not protect against STDs, so she could have acquired tubal damage during the decade of use 3

4. Diminished Ovarian Reserve 3

• Age-related if she is now in her mid-to-late 30s (started at ~20 years old, used for 10 years)
• Women over 30 years had significantly longer time-to-conception intervals after implant removal compared to younger women 2
• Assess with day 3 FSH, AMH, antral follicle count 3

5. Uterine Pathology 3

• Fibroids, polyps, intrauterine adhesions (Asherman syndrome), adenomyosis 3
• Congenital uterine anomalies (septate uterus, bicornuate uterus) 3
• These would not be caused by Nexplanon but may have been present and undiagnosed 3

6. Cervical Factor 3

• Cervical stenosis, inadequate cervical mucus, prior cervical procedures (LEEP, cone biopsy) 3
• Less common but should be considered 3

7. Endometriosis 3

• May have been present before Nexplanon use 3
• Nexplanon may have suppressed symptoms (dysmenorrhea, pelvic pain) during use, masking the diagnosis 4

Critical Pitfalls to Avoid

• Do not attribute infertility to Nexplanon use: The evidence clearly shows rapid return to normal fertility after removal 1, 2, 5
• Do not delay male factor evaluation: Obtain semen analysis immediately, as this is the simplest and most cost-effective initial test 2
• Do not assume regular cycles: Ten years of Nexplanon-induced amenorrhea or irregular bleeding may have masked pre-existing ovulatory dysfunction 3
• Consider age-related factors: If she started Nexplanon at age 20 and used it for 10 years, she is now 30+ years old, and age-related fertility decline becomes relevant 2

Immediate Evaluation Priorities

• Confirm ovulation: Basal body temperature charting, mid-luteal progesterone, or ovulation predictor kits 3
• Semen analysis for partner: This should be done early, not as a last resort 2
• Assess tubal patency: Hysterosalpingography (HSG) if indicated by history 3
• Ovarian reserve testing: Particularly if age >35 years 3
• Screen for thyroid dysfunction, hyperprolactinemia: Basic hormonal workup 3

The key message: Nexplanon itself is not the cause of her infertility 1, 2, 5. The differential diagnosis should focus on the standard causes of infertility that may have been present before contraceptive use or developed independently during the 10-year period.