Recurrent Pregnancy Loss: Causes, Diagnosis & Treatment

13 Apr Recurrent Pregnancy Loss: Causes, Diagnosis & Treatment

Recurrent pregnancy loss is one of the most heartbreaking experiences a couple can face. Each loss carries its own grief and when it happens again and again, the pain compounds with confusion, fear, and an urgent need for answers. If you have experienced two or more miscarriages, you are not alone, and you are not without options.

Recurrent pregnancy loss affects approximately 1–2% of couples trying to conceive. While each individual pregnancy loss is common occurring in up to 15–20% of confirmed pregnancies — recurrent pregnancy loss is a distinct clinical condition that warrants thorough investigation and targeted treatment. After two losses, the risk of a third rises significantly, which is why specialist evaluation must not be delayed.

At Fertibless Clinic in Delhi, Dr. Shipra Gupta approaches recurrent pregnancy loss with a comprehensive, evidence-based investigation protocol because finding the cause is the most important step toward achieving a successful pregnancy.

Defining Recurrent Pregnancy Loss

Recurrent pregnancy loss is generally defined as two or more clinical pregnancy losses before 20 weeks of gestation. Some older guidelines required three losses before initiating investigation, but most specialist centres including Fertibless Clinic now recommend investigating after two losses, particularly when the woman is over 35 or when the losses are associated with other risk factors such as late timing or prior treatment.

Recurrent pregnancy loss is not the same as biochemical pregnancy loss, which refers to a positive test followed by early bleeding before a clinical pregnancy is confirmed on ultrasound. Both are distressing, but the investigation pathways differ.

What Causes Recurrent Pregnancy Loss?

Recurrent pregnancy loss is rarely due to a single cause. In most couples, it is multifactorial several overlapping factors elevating risk together. The main categories include:

Chromosomal Abnormalities in the Embryo

The most common cause of any single miscarriage and a significant contributor to recurrent pregnancy loss is chromosomal abnormality in the embryo. When an egg or sperm carries an incorrect number of chromosomes, the resulting embryo cannot develop normally and the pregnancy ends. This risk increases substantially with advancing maternal age. In couples experiencing recurrent pregnancy loss, chromosomally abnormal embryos are identified as the primary cause in approximately 50–60% of cases.

Uterine Structural Abnormalities

Physical abnormalities of the uterine cavity are a well-recognised cause of recurrent pregnancy loss:

• Uterine septum — The most common anatomical cause of recurrent pregnancy loss. A fibrous band dividing the uterine cavity reduces blood supply to the implanting embryo, causing loss typically in the first trimester.
• Submucosal fibroids — Fibroids protruding into the uterine cavity disrupt the endometrial surface needed for healthy implantation.
• Intrauterine adhesions (Asherman’s syndrome) — Scar tissue from previous procedures impairs endometrial development and blood flow.
• Congenital uterine anomalies — Unicornuate or bicornuate uterus are associated with both recurrent pregnancy loss and preterm birth.

Antiphospholipid Syndrome (APS)

APS is one of the most important and treatable causes of recurrent pregnancy loss. This autoimmune condition causes the body to produce antibodies that promote blood clotting in placental vessels restricting blood flow to the developing baby and causing pregnancy loss, typically in the second trimester. Treatment with low-dose aspirin and low molecular weight heparin reduces recurrent pregnancy loss risk in APS by approximately 50–60%.

Hormonal and Endocrine Factors

• Thyroid dysfunction — Both overt and subclinical hypothyroidism are associated with increased recurrent pregnancy loss risk. TSH should be optimised below 2.5 mIU/L before conception.
• Poorly controlled diabetes — Elevated blood glucose increases chromosomal abnormality risk and impairs implantation.
• Luteal phase deficiency — Insufficient progesterone production after ovulation may impair endometrial support for early pregnancy.
• PCOS — Elevated androgens and insulin resistance are associated with higher rates of recurrent pregnancy loss in some women.

Thrombophilias

Inherited clotting disorders — such as Factor V Leiden or prothrombin gene mutation — may cause placental blood clots in susceptible women, contributing to recurrent pregnancy loss. Evaluation is recommended as part of a complete workup, though treatment evidence is more variable than for APS.

Parental Chromosomal Anomalies

In approximately 3–5% of couples with recurrent pregnancy loss, one partner carries a balanced chromosomal rearrangement — typically a translocation. The carrier parent is unaffected, but embryos may inherit an unbalanced chromosomal complement, causing miscarriage. Karyotyping of both partners identifies this important cause of recurrent pregnancy loss.

Male Factor — Sperm DNA Fragmentation

Sperm DNA fragmentation is increasingly recognised as a significant contributor to recurrent pregnancy loss. Damaged sperm DNA may allow fertilisation but impairs embryo development — leading to early arrest and pregnancy loss. This is not detected by standard semen analysis, making specific DNA fragmentation testing essential in all couples with recurrent pregnancy loss.

How Recurrent Pregnancy Loss Is Investigated

A comprehensive recurrent pregnancy loss investigation at Fertibless Clinic includes:

• APS Screen: Antiphospholipid antibody panel — Lupus anticoagulant, anticardiolipin antibodies, and anti-beta2-glycoprotein I. Two positive results 12 weeks apart are required for APS diagnosis.
• Thyroid: Thyroid function tests — TSH, Free T4, and thyroid peroxidase (TPO) antibodies to identify both overt and autoimmune thyroid conditions contributing to recurrent pregnancy loss.
• Karyotyping: Karyotyping of both partners — Identifies balanced chromosomal rearrangements such as translocations that cause recurrent pregnancy loss through unbalanced embryo inheritance.
• Uterine Scan: Uterine cavity assessment — Saline infusion sonography (SIS), 3D ultrasound, or hysteroscopy to detect structural anomalies. Hysteroscopy is both diagnostic and therapeutic for polyps, adhesions, and septa.
• Thrombophilia: Thrombophilia screen — Factor V Leiden, prothrombin gene mutation, protein C and S, antithrombin III levels.
• Blood Sugar: Fasting blood glucose and HbA1c — To identify undiagnosed or poorly controlled diabetes.
• Sperm DNA: Sperm DNA Fragmentation Index (DFI) — A DFI above 25–30% is associated with recurrent pregnancy loss even when all other semen parameters are normal.
• Immune Testing: Uterine NK cell testing — Elevated natural killer cell activity in the uterine lining is being studied as a factor in unexplained recurrent pregnancy loss at specialist centres.

Treatment Approaches for Recurrent Pregnancy Loss

Treatment for recurrent pregnancy loss is targeted to identified causes where possible — and evidence-based empirical treatment is used when investigations do not reveal a specific cause:

• APS: APS — Low-dose aspirin from the time of a positive pregnancy test, combined with low molecular weight heparin injections throughout pregnancy. This is the single most evidence-supported treatment for recurrent pregnancy loss.
• Structural: Uterine structural abnormalities — Hysteroscopic resection of septa, polyps, fibroids, or adhesions. Correction of a uterine septum alone has been shown to substantially reduce recurrent pregnancy loss rates in affected women.
• Thyroid: Thyroid optimisation — Levothyroxine treatment to bring TSH below 2.5 mIU/L before conception, with dose adjustment as soon as pregnancy is confirmed.
• Sperm DNA: High sperm DNA fragmentation — Antioxidant treatment, lifestyle modification (stopping smoking, reducing alcohol), and in some cases ICSI with surgically retrieved sperm, which carries lower DNA damage.
• IVF + PGT-A: IVF with PGT-A — The most powerful intervention for couples where chromosomal embryo abnormalities are driving recurrent pregnancy loss. Only euploid embryos are transferred, dramatically reducing the risk of further recurrent pregnancy loss from chromosomal causes.
• Progesterone: Progesterone supplementation — Vaginal progesterone in early pregnancy is widely used in recurrent pregnancy loss, particularly where luteal phase deficiency is suspected. The PRISM trial supports its use in women with a history of three or more losses.

Expert Insight — Dr. Shipra Gupta Recurrent pregnancy loss is one of the most emotionally devastating things I see in my clinic — and my first commitment to every couple who has experienced it is this: we will investigate completely. Not just the standard tests, but the full picture — APS, sperm DNA, the uterine cavity, the chromosomes of both partners, the immune environment. In many couples, we do find a treatable cause. And even when we do not find a specific cause, IVF with genetic testing of embryos has genuinely transformed outcomes for couples with recurrent pregnancy loss — giving them the ability to transfer only chromosomally healthy embryos and break the cycle of loss. — Dr. Shipra Gupta, Infertility Specialist, Fertibless Clinic, Delhi

Emotional Support Through Recurrent Pregnancy Loss

The psychological burden of recurrent pregnancy loss is profound and often underestimated. Research shows that women experiencing recurrent pregnancy loss report levels of anxiety and depression comparable to those with serious medical diagnoses. Grief after pregnancy loss is real and valid — and it does not diminish with each subsequent loss. In many cases, it compounds.

At Fertibless, emotional support is considered an integral part of recurrent pregnancy loss care — not an add-on. Couples are encouraged to access fertility counselling, peer support communities, and to communicate openly with Dr. Shipra Gupta and the care team throughout the investigation and treatment process.

Reference: Royal College of Obstetricians and Gynaecologists (RCOG) — Recurrent Miscarriage Guidelines — www.rcog.org.uk | ASRM Practice Guidelines — www.asrm.org | WHO — www.who.int

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