By Dr. Shweta Agarwal, MBBS, DGO Medically reviewed by Dr. Shweta Agarwal, MBBS, DGO Last updated: June 2026
Information on this page is educational and does not replace a medical consultation. Outcomes depend on individual clinical factors.
Aansh Hospital & IVF Center is a government-registered Level-2 ART clinic (Reg. No. MH/AC/2024/15441/L2/Chandrapur/132), part of a growing chain of fertility centers across Vidarbha and northern Telangana, with our headquarters and in-house embryology lab in Chandrapur. Our government ART registration covers the full range of regulated fertility diagnostic and treatment services, under the clinical leadership of Dr. Shweta Agarwal and embryology led by Aayush Agarwal, Ph.D..
If you are reading this after more than one pregnancy loss, I want to begin with something that is rarely said clearly enough: what you are carrying — the grief, the confusion, the particular exhaustion of hoping again and losing again — is real and serious, and it is not something to just push through. Recurrent pregnancy loss is one of the most emotionally heavy experiences a couple can face in reproductive medicine. The body keeps doing something that the heart keeps hoping will not happen again.
This guide is written for the person who is past the acute stage of loss and is starting to ask: what should I be investigating? What tests actually matter? What can be treated? I will try to answer those questions clearly and honestly — including, importantly, being honest about what the evidence does and does not support.
The workup for recurrent pregnancy loss is not a simple checklist. It is a clinical conversation. But knowing the categories in advance — what each investigation is looking for and why — means you can have that conversation as an informed participant rather than a passive recipient.
What counts as recurrent pregnancy loss, and when should the workup begin?
Recurrent pregnancy loss is most commonly defined as two or more consecutive pregnancy losses before 20 weeks of gestation. Some guidelines have historically required three losses before formal investigation; others now recommend starting after two, particularly when the woman is older or when there are additional risk factors.
In practice, many clinicians — including the approach at Aansh — will begin a discussion of investigation after two losses, because the emotional cost of waiting for a third is significant, and because some causes (antiphospholipid syndrome, for example) are treatable and worth identifying early.
Earlier investigation is also reasonable — regardless of the number of losses — when the woman is over 35, when there is a known uterine abnormality, or when other risk factors are present. This is a conversation worth having with your clinician based on your specific situation.
One important truth to hold throughout this process: in roughly half of couples investigated for recurrent pregnancy loss, no specific cause is found after a complete workup. That is not a failure of the investigation — it reflects the biological reality that many early pregnancy losses are caused by random chromosomal events in an individual pregnancy that do not indicate a recurring problem in either partner. Many couples in this situation — those with unexplained RPL — go on to have a successful pregnancy. We cannot predict this in individual cases, and we make no promises. But the overall picture for unexplained RPL is not as bleak as the experience of repeated losses may make it feel.
What is the genetic investigation in recurrent miscarriage — and why is it about chromosomes, not sex?
The genetic investigation in recurrent pregnancy loss has two components: testing the parents, and where possible, testing the pregnancy itself.
Parental karyotyping means taking a blood sample from both partners and looking at the chromosomes — specifically for balanced translocations. A balanced translocation is a structural rearrangement in which two chromosomes have swapped segments. The person carrying the translocation is typically unaffected because no genetic material is lost — it is just rearranged. However, when they produce eggs or sperm, the rearrangement can result in embryos that receive an unbalanced set of chromosomes, which often leads to miscarriage. Parental karyotyping is recommended for both partners in the RPL workup because either can carry a translocation. It is a one-time test and does not change over time.
Genetic testing of pregnancy tissue (products of conception) — where the tissue from a miscarriage is sent for chromosomal analysis — can tell you whether that specific loss was caused by a chromosomal abnormality in the pregnancy. If the pregnancy tissue shows an abnormality (such as trisomy), that points toward a random event rather than a recurring structural cause in the parents. If it shows a normal chromosomal result, that raises the question of what else might have caused the loss and strengthens the case for investigating other categories.
A very important clarification: chromosomal testing of pregnancy tissue is about identifying whether the embryo had a chromosomal imbalance — conditions that affect whether a pregnancy can develop to term. It is entirely separate from, and never used for, determining the sex of a pregnancy. The PCPNDT Act prohibits sex determination, and this testing is not, and never should be, framed that way. The clinical purpose is chromosomal health — full stop.
Similarly, preimplantation genetic testing (PGT) for couples using IVF — which screens embryos for chromosomal abnormalities before transfer — is a chromosomal health tool, not a sex-selection tool. This distinction matters legally and ethically, and it is the only framing used at Aansh.
What uterine and anatomical investigations are recommended?
Structural abnormalities of the uterus can prevent a pregnancy from implanting or developing normally. This category of investigation is one of the more actionable areas of the RPL workup, because many uterine causes are surgically correctable.
The standard uterine investigations include:
Pelvic ultrasound — a baseline assessment of the uterine shape, size, and the uterine cavity. It can identify fibroids (particularly submucous fibroids that protrude into the cavity), large polyps, and some major structural abnormalities. A basic ultrasound, however, has limitations in evaluating the cavity in detail.
Saline infusion sonography (saline sonohysterography) or hysteroscopy — these provide a more detailed view of the uterine cavity. Saline sonography instills saline into the cavity during ultrasound to outline its shape. Hysteroscopy uses a thin camera inserted through the cervix to look directly inside the uterus. Both are better than standard ultrasound alone for detecting:
- A uterine septum — a fibrous or muscular band that divides the uterine cavity. This is the most common surgically correctable cause of recurrent miscarriage. A septum can reduce the available space for a pregnancy and impair blood supply to the implantation site. Septum resection via hysteroscopy (hysteroscopic metroplasty) is well-established and generally straightforward.
- Intrauterine adhesions (Asherman's syndrome) — scar tissue within the cavity, often from previous uterine procedures.
- Submucosal fibroids or polyps that were not visible on standard ultrasound.
- Bicornuate or arcuate uterus — other congenital shapes of the uterine cavity that may contribute to pregnancy loss.
Which test is used — saline sonography or hysteroscopy — depends on what the ultrasound showed, the clinician's assessment, and the local availability. Hysteroscopy has the advantage of being diagnostic and potentially therapeutic in the same procedure.
What endocrine tests are part of the recurrent miscarriage workup?
Several hormonal conditions are associated with recurrent pregnancy loss, and most are treatable when identified.
Thyroid function — TSH and thyroid antibodies. Both hypothyroidism (underactive thyroid) and thyroid antibody positivity (even with normal TSH) have been associated with pregnancy loss. Thyroid-stimulating hormone (TSH) is the primary screening test; thyroid peroxidase antibodies (TPO antibodies) are also checked. Thyroid disorders are very common in Indian women and are straightforward to treat with levothyroxine before and during pregnancy. Getting thyroid function into a well-controlled range before attempting conception is a clear, actionable step.
Prolactin. Elevated prolactin (hyperprolactinaemia) can interfere with ovulation and luteal phase function. If elevated, it is treatable with medication. It is a standard part of the endocrine screen.
Blood glucose / diabetes screening. Poorly controlled diabetes — particularly if undiagnosed before pregnancy — is associated with both early pregnancy loss and complications. Fasting blood glucose, HbA1c, or a glucose tolerance test may be included depending on the clinical picture.
PCOS-related hormonal evaluation. Polycystic ovary syndrome (PCOS) is associated with insulin resistance and elevated androgens, both of which have been linked to pregnancy loss. If PCOS has not been previously evaluated, the RPL workup is a reasonable time to assess it, particularly if the clinical picture (irregular cycles, other features) is suggestive.
What is antiphospholipid syndrome, and why does it matter most in the RPL workup?
Antiphospholipid syndrome (APS) is the most firmly established treatable cause of recurrent pregnancy loss. It is an autoimmune condition in which the immune system produces antibodies that increase the tendency of blood to clot inappropriately — which can interrupt placental blood flow and cause miscarriage, most commonly in the second trimester but also in the first.
The antibodies tested for in the standard APS screen are:
- Lupus anticoagulant (LA)
- Anticardiolipin antibodies (aCL) — IgG and IgM
- Anti-beta-2-glycoprotein-1 antibodies (anti-β2GP1) — IgG and IgM
A positive result needs to be confirmed on a repeat test at least 12 weeks later — because a transient positive (due to acute illness, for example) is not clinically significant. APS is diagnosed only when the antibodies are persistently positive.
The treatment for APS in pregnancy is well-established: low-dose aspirin started before conception or early in pregnancy, plus low-molecular-weight heparin (LMWH) injections during pregnancy, under specialist supervision. This is one of the clearer examples in reproductive medicine where a treatable cause can be identified and a specific intervention meaningfully changes the outcome — though even with treatment, outcomes vary by individual and no outcome can be guaranteed.
If you have had recurrent losses, particularly second-trimester losses or losses with features of placental dysfunction, APS testing is among the most important investigations to ensure has been done.
वारंवार गर्भपात (recurrent pregnancy loss, as it is known in Marathi and Hindi) carries a weight that is disproportionate to how often it is discussed. APS is the kind of diagnosis that couples sometimes go several losses without having tested — and it is one where the knowledge genuinely changes the plan.
What about other clotting (thrombophilia) tests — are they all evidence-based?
Beyond APS, there is a broader category of inherited thrombophilias — genetic clotting tendencies such as Factor V Leiden mutation, prothrombin gene mutation, protein C and S deficiency, and MTHFR variants. Testing for these is sometimes included in RPL workups, but the evidence is more mixed than for APS.
The link between inherited thrombophilias and recurrent first-trimester miscarriage (as opposed to late pregnancy loss or stillbirth) is not as clearly established as for APS. Some guidelines do not routinely recommend thrombophilia testing for first-trimester RPL unless the history includes second-trimester losses or other specific features.
This is an area where the clinical picture matters. Over-testing — ordering every available panel without clear clinical indication — can generate results (like MTHFR heterozygosity, which is very common in the general population) that lead to unnecessary anxiety and empirical treatments that lack a solid evidence base. A clinician who explains which tests are being ordered and why is preferable to one who orders a blanket panel.
When is the male partner investigated in recurrent pregnancy loss?
Recurrent pregnancy loss has historically been framed as a female-factor condition, but there is increasing evidence that sperm quality can contribute — specifically, sperm DNA fragmentation.
Standard semen analysis measures sperm count, motility, and morphology. It does not assess the integrity of the DNA within the sperm. Elevated sperm DNA fragmentation means the genetic material carried by the sperm has increased strand breaks. Fertilisation can still occur — hence the couple experiences confirmed pregnancies — but early development may be disrupted, leading to pregnancy loss.
Sperm DNA fragmentation testing is not universally included in all RPL workups, but it is increasingly considered, particularly in couples where:
- The female-partner workup is largely normal
- There have been multiple early losses
- There is also a history of poor embryo development in IVF
If elevated, there are approaches to consider — including antioxidant supplementation, lifestyle modification, or in the context of IVF, the use of testicular sperm rather than ejaculated sperm (which typically has lower fragmentation levels). Embryology at Aansh is led by Aayush Agarwal, Ph.D., who can advise on whether fragmentation testing is relevant to your specific situation.
What is actually treatable — and what has limited evidence?
One of the most useful things to understand before starting the RPL workup is which findings lead to interventions with reasonable evidence behind them, and which interventions are less well-supported.
Well-established treatments:
- APS → aspirin + LMWH during pregnancy under specialist supervision
- Thyroid dysfunction → levothyroxine to optimise TSH levels
- Hyperprolactinaemia → dopamine agonist medication (e.g. cabergoline)
- Uterine septum → hysteroscopic resection
- Submucosal fibroids / polyps → hysteroscopic removal
- Poorly controlled diabetes → optimisation before and during pregnancy
- PCOS with metabolic dysfunction → metabolic optimisation, weight management where indicated, and management of insulin resistance
Areas where the evidence is more limited or evolving:
- Empirical treatments (steroids, progesterone, intravenous immunoglobulin, heparin without APS diagnosis) given without an identified cause lack consistent evidence of benefit. This is not to say they are never used, but the conversation with your clinician should include what the evidence base is.
- Routine testing for natural killer (NK) cells or complex immunological panels in unexplained RPL — while discussed in specialist settings — lacks established evidence to support widespread clinical use.
- MTHFR heterozygosity alone, in the absence of other thrombophilia findings, is generally not considered a clinically significant cause of RPL in current guidance.
The goal of this note is not to discourage investigation but to help you ask good questions: what specifically are we testing for, and what is the treatment pathway if it comes back positive?
How does IVF with PGT relate to recurrent pregnancy loss?
For couples where a chromosomal cause has been identified — particularly a parental balanced translocation — or for couples with unexplained RPL who have not responded to other management, IVF with preimplantation genetic testing (PGT) is sometimes discussed.
PGT involves creating embryos through IVF, then biopsying each embryo at the blastocyst stage to test for chromosomal abnormalities before transfer. The aim is to identify embryos that are chromosomally normal, reducing the risk that a transfer will result in a chromosomally abnormal pregnancy that miscarries.
This is not the right path for every couple with RPL — it requires IVF, it adds cost, and it does not address non-chromosomal causes of loss. It is most clearly indicated where a parental structural chromosomal abnormality (such as a balanced translocation) is identified, or where repeated losses with known chromosomal abnormality in the pregnancy tissue suggest a pattern. The decision to pursue IVF+PGT should be based on a thorough review of the couple's specific history and investigation results.
Our costs and EMI options include transparent ranges for IVF and genetic testing; final costs depend on individual clinical evaluation.