Diagnosis of mittelschmerz is generally made if a woman is mid-cycle and a pelvic examination shows no abnormalities. If the pain is prolonged and/or severe, other diagnostic procedures such as an abdominal ultrasound may be performed to rule out other causes of abdominal pain.

The pain of mittelschmerz is sometimes mistaken for appendicitis and is one of the differential diagnoses for appendicitis in women of child-bearing age.

Women charting with some form of fertility awareness may find mittelschmerz to be a helpful secondary sign in detecting ovulation. Because normal sperm life is up to five days, however, mittelschmerz alone does not provide sufficient advance warning to avoid pregnancy. Because other causes of minor abdominal pain are common, mittelschmerz alone also cannot be used to confirm the beginning of the post-ovulatory infertile period.

Symptoms-based methods of fertility awareness may be used to detect ovulation or to determine that cycles are anovulatory. Charting of the menstrual cycle may be done by hand, or with the aid of various fertility monitors. Records of one of the primary fertility awareness signs—basal body temperature—can detect ovulation by identifying the shift in temperature which takes place after ovulation. It is said to be the most reliable way of confirming whether ovulation has occurred.

Women may also use ovulation predictor kits (OPKs) which detect the increase in luteinizing hormone (LH) levels that usually indicates imminent ovulation. For some women, these devices do not detect the LH surge, or high levels of LH are a poor predictor of ovulation; this is particularly common in women with PCOS. In such cases, OPKs and those fertility monitors which are based on LH may show false results, with an increased number of false positives or false negatives. Dr Freundl from the University of Heidelberg suggests that tests which use LH as a reference often lack sensitivity and specificity.

The European Society of Human Reproduction and Embryology (ESHRE) notes that the aim of ovulation induction should be mono-ovulation and not over-stimulation of the ovaries . The risks associated with multiple pregnancy are much higher than singleton pregnancy; incidences of perinatal death are seven times higher in triplet births and five times higher in twin births than the risks associated with a singleton pregnancy. It is therefore important to adapt the treatment to each individual patient.

Women with polycystic ovary syndrome may be particularly at risk. Multiple pregnancy occurs in approximately 15-20% of cases following cycles induced with gonadotrophins such as hMG and FSH induced ovulations.

During ovulation induction, it is recommended to start at a low dose and monitor the ovarian response with vaginal ultrasound, including discernment of the number of developing follicles. A cycle with supernumerary follicles is usually defined as one where there are more than two follicles >16 mm in diameter. It is generally recommended to have such cycles cancelled because of the risk of multiple pregnancy. In cancelled cycles, the woman or couple should be warned of the risks in case of supernumerary follicles, and should avoid sexual intercourse or use contraception until the next menstruation. Induction of final maturation (such as done with hCG) may need to be withheld because of increased risk of ovarian hyperstimulation syndrome(OHSS). The starting dose of the inducing drug should be reduced in the next cycle.

Alternatives to cancelling a cycle are mainly:

- Aspiration of supernumerary follicles until one or two remain.

- Converting the protocol to IVF treatment with embryo transfer of up to two embryos only.

- Selective fetal reduction. This alternative confers a high risk of complications.

- Proceeding with any multiple pregnancy without fetal reduction, with the ensuing risk of complications. This alternative is not recommended.

MRI use has become increasingly common for diagnosis of appendicitis in children and pregnant patients due to the radiation dosage that, while of nearly negligible risk in healthy adults, can be harmful to children or the developing fetus. In pregnancy, it has been found to be more useful during the second and third trimester, particularly as the enlargening uterus displaces the appendix, making it difficult to find by ultrasound. The periappendiceal stranding that is reflected on CT by fat stranding on MRI appears as increased fluid signal on T2 weighted sequences. First trimester pregnancies are usually not candidates for MRI, as the fetus is still undergoing organogenesis, and there are no long-term studies to date regarding its potential risks or side effects.

The definitive diagnosis is based on pathology. The histologic finding of appendicitis is neutrophilic infiltrate of the muscularis propria.

Periappendicitis, inflammation of tissues around the appendix, is often found in conjunction with other abdominal pathology.