Reproduction in humans is not perfect. Abnormalities can and do occur after fertilization of an egg by sperm. One of the most serious abnormalities is an ectopic pregnancy. In this situation the fertilized egg does not implant in the uterine endometrial cavity but attaches to another area of the reproductive tract or in some cases into other abdominal organs. The fertilized zygote starts to develop but it cannot grow normally. In the United States of America, one to two out of every 100 pregnancies is an ectopic pregnancy. Since there are 5.3 to 6.3 million pregnancies each year this means that there will be 53,000 to 63,000 ectopic pregnancies. Ectopic pregnancies are life-threatening unless they are treated appropriately. The definition of an ectopic pregnancy is a gestational sac implanted in an anatomical location that is not the uterine cavity (1). 97% of the time this location is the fallopian tube (2). Other anatomical locations are a Cesarean Sections Scar on the anterior wall of the uterus, the mucosa of the cervix, the ovary and even abdominal organs such as bowel, rectum or spleen. In rare cases an intrauterine pregnancy and an ectopic pregnancy exist together; a situation called heterotrophic pregnancy. When studied under a microscope, chorionic villi and embryonic tissue at the site is noted often along with red blood cells and inflammatory cells. When these are observed a diagnosis is definitive. A rupture of an ectopic pregnancy in a fallopian tube causes massive hemorrhage. This situation is the leading cause of first trimester maternal mortality. Rupture of an ectopic is stated to be 9 to 14% of all ectopic pregnancies. It is stated to be 5-10% of all pregnancy related deaths by one source (1). Others give an estimate of 2.7% of all pregnancy related deaths (2). In western countries with good health care systems the overall rate of ruptured ectopic pregnancy is said to be 15% (1). The rate of ectopic implantation in pregnancy is increased after in-vitro fertilization (IVF). This rate is 2.1-8.6% compared to 2% in natural conception (1). Conception occurring with an IUD increases the risk of an ectopic pregnancy and the use of progesterone only contraception is associated with an increased risk of ectopic pregnancy as well (3). Risk factors are prior ectopic pregnancy, prior pelvic surgery, damage to the fallopian tube, pelvic infection, endometriosis, variant reproductive tract anatomy, history of infertility (1).
What causes a fertilized egg to implant in an abnormal location? The fallopian tube may be damaged by prior infection such as gonorrhea, chlamydia, or other bacteria causing pelvic inflammation. The tube is scared and cilia that normally propel the fertilized egg toward the uterine cavity are dysfunctional (1)(4). Other risks of an ectopic are exposure of a women during her own gestation in her mother’s uterus to diethylstilbesterol.
Symptoms of an ectopic pregnancy are variable and begin in ways that can make a diagnosis difficult. There is usually a colicky pain or pelvic discomfort on one side of the abdomen. There is often a history of delayed menstrual period but vaginal bleeding accompanying the implantation may confuse this history. It a rupture occurs the woman will experience generalized lower abdominal pain, shoulder pain and rectal pressure perhaps along with urinary symptoms. However, not all individuals report all of these symptoms.
Ectopic pregnancy mimics many other diagnostic conditions such as: ovarian torsion, tubo-ovarian abscess, appendicitis, hemorrhagic corpus luteum of the ovary, ruptured ovarian cyst, spontaneous abortion (miscarriage) incomplete spontaneous abortion (incomplete miscarriage) pelvic inflammatory disease, and ureteral calculi (stones). In geographical areas without well-trained medical personnel an individual with these symptoms might not be appropriately cared for. Therefore, the life of the women is put at serious risk. This situation exists in many rural areas where hospitals and emergency rooms have closed. It can be difficult in very early pregnancy to determine if the correct diagnosis is an ectopic or an intrauterine pregnancy. There are reports in the medical literature of delay in diagnosis and treatment by clinicians in states where there are currently strict induced abortion bans due to this uncertainty. This delay can make treatment more difficult and can further risk the life of the woman.
The appropriate evaluation of a woman with symptoms of suspected ectopic pregnancy is the assessment of serum β-hCG (β human chorionic gonadotropin) levels and ultrasound imaging. A transvaginal ultrasound is the most accurate and sensitive imaging technique for making an early diagnosis (2). Transvaginal ultrasound will visualize a small gestational sac within the uterus in the decidual lining (the endometrium of pregnancy) in a normal pregnancy at 5 weeks gestational age. A ring of tissue is often seen around the sac. At 6 weeks gestational age an embryonic pole is noted with transvaginal ultrasound. Used along with the β-hCG level it is very informative (2). The objective is to make the diagnosis of an ectopic pregnancy before a rupture occurs. When a β-hCG level is ≥2000 mIU/mL and no evidence of a intrauterine pregnancy is observed on ultrasound an ectopic pregnancy is highly likely. The American College of Obstetricians and Gynecologists state that to be completely certain the level should be 3500 mIU/mL. If the woman is stable, she is followed with serial β-hCG levels until the diagnosis is clear. For instance, if the β-hCG level is ≤ 1500 mIU/mL it usually will rise 48% or more over 48 hours. It rises more slowly in the case of an ectopic pregnancy. In this case it rises only about 21% in 48 hours. When serial β-hCG levels decrease over time a pregnancy loss has occurred. If the diagnosis is not clear MRI imaging is used. Obviously if the woman shows signs and symptoms of rupture treatment is initiated immediately. Early detection of a Cesarean Scare ectopic is challenging. Transvaginal ultrasound with color Doppler is helpful as is MRI imaging. Ectopic pregnancy with an abdominal implantation is known to develop to the third trimester and as far a term gestation. Delivery is by Cesarean Section. There is may be extensive hemorrhage at the time of delivery. In must be noted that abdominal pregnancy is extremely rare. I have only seen one case in my whole active career in obstetrics and gynecology.
The treatment of ectopic pregnancy depends on the women’s symptoms and diagnostic findings. Subsequent fertility is highest in women who are treated if appropriate with methotrexate. This is a folate antagonist that disrupts rapidly dividing cells. However, if the β-hCG level is on the higher side this treatment is less effective (2). Since methotrexate is used to induce termination of intrauterine pregnancy and since the overturn of Roe vs. Wade there have been officials in some states and the federal government who seek to limit the availability of this drug. It is important for the public to know that the drug is used in the treatment of ectopic pregnancy and thus it is vital to be readily available for use. The highest successful treatment is surgical intervention. Usually, the surgery is accomplished by laparoscopic surgery.
Reproductive scientists have studied the biochemical molecules that are associated with implantation of the human zygote on the tissues surrounding ectopic pregnancies. One study showed that KISS1/Kisspeptin is down-regulated in early ectopic pregnancy. These studies suggest that the down-regulation occurs by a repressive interaction with miR-324-3p. These molecules are increased in normal intrauterine pregnancies (5). Other research studied suggest that a number of other molecules are dysregulated as well (6, 7). These are Activin A-B, ADAM-12, (A disintegrin and metalloproteinase -12) , micro-RNA- 378d , PAPP-A (Pregnancy -associated plasma protein A). Progesterone levels in serum are also lower in women with ectopic pregnancies.
In summary, ectopic pregnancy is a pregnancy that develops in an anatomical location outside of the uterine cavity. The fertilized egg is not able to grow normally. Most importantly, ectopic pregnancies pose a serious life-threatening risk to the life of the mother. Because one to two out of every 100 pregnancies is an ectopic it is vital that the maternal health care system provides access in all areas of the country to safe diagnosis and treatment in all areas, to ensure that needless maternal deaths are prevented. Additional research along with the development of AI methods will help with early diagnosis. Finally, education of young women of the risk factors for ectopic pregnancy and the early symptoms are extremely important in assuring good pregnancy outcomes.
References and further reading:
(1).Mullany K, Minneci M, Monjazeb R, C Coiado O. Overview of ectopic pregnancy diagnosis, management, and innovation. Womens Health (Lond). 2023 Jan-Dec;19:17455057231160349. doi: 10.1177/17455057231160349. PMID: 36999281; PMCID: PMC10071153.
(2). Vadakekut E, Gnugnoli DM. Ectopic Pregnancy. StatPearls (Internet) NCBI Bookshelf.. March 27, 2025. Accessed January 7, 2026.
(3) .Hayashi T, Sano K, Konishi I. Histopathological Findings of Ectopic Pregnancy in Contraceptive-Wearing Woman. J Clin Med Res. 2023 Jul;15(7):384-389. doi: 10.14740/jocmr4924. Epub 2023 Jul 12. PMID: 37575351; PMCID: PMC10416193.
(4). Russell JB. The etiology of ectopic pregnancy. Clin Obstet Gynecol. 1987 Mar;30(1):181-90. doi: 10.1097/00003081-198703000-00025. PMID: 2953513.
(5). Romero-Ruiz A, Avendaño MS, Dominguez F, Lozoya T, Molina-Abril H, Sangiao-Alvarellos S, Gurrea M, Lara-Chica M, Fernandez-Sanchez M, Torres-Jimenez E, Perdices-Lopez C, Abbara A, Steffani L, Calzado MA, Dhillo WS, Pellicer A, Tena-Sempere M. Deregulation of miR-324/KISS1/kisspeptin in early ectopic pregnancy: mechanistic findings with clinical and diagnostic implications. Am J Obstet Gynecol. 2019 May;220(5):480.e1-480.e17. doi: 10.1016/j.ajog.2019.01.228. Epub 2019 Jan 29. PMID: 30707968.
(6). Refaat B. Role of activins in embryo implantation and diagnosis of ectopic pregnancy: a review. Reprod Biol Endocrinol. 2014 Nov 25;12:116. doi: 10.1186/1477-7827-12-116. PMID: 25421645; PMCID: PMC4254208
(7). Hou L, Liang X, Zeng L, Wang Q, Chen Z. Conventional and modern markers of pregnancy of unknown location: Update and narrative review. Int J Gynaecol Obstet. 2024 Dec;167(3):957-967. doi: 10.1002/ijgo.15807. Epub 2024 Jul 18. PMID: 39022869.