A framework for understanding your fertility
Most people who want to have a baby will. But when it's not happening — or when you want to understand your landscape before you start — the standard system isn't designed to help you. It's designed around trial and error: try, fail, test for one thing, try again. That process costs time and money, and for many people, both are limited.
This is a map. Six biological systems have to work, and a set of inputs affect all of them. Nearly everything here can be investigated before you start trying — but the standard system won't let you look until something has gone wrong. The question is: what do you want to know before you start, versus what are you willing to discover along the way?
Click any section below to expand it. Go as deep as you want.
Inputs: What Affects the Whole Chain
| What it affects | On track | Needs attention | Needs action | Notes |
|---|---|---|---|---|
| Egg quality (Factors 1 & 4) |
Under 35: ~60-65% of embryos chromosomally normal | 35-37: ~50% normal 38-40: ~35% normal |
40+: ~20-30% normal, declining steeply after 42 | This is why fertility declines with age — not because you run out of eggs, but because more of them have the wrong number of chromosomes. At 30, about a third have this problem. By 40, it's the majority. |
| Ovarian reserve (Factor 1) |
AMH typically higher, AFC higher | Reserve declining; may still look adequate but with less margin | Significantly diminished. Fewer eggs per cycle, less time to act. | See the age-adjusted AMH chart in Factor 1. Reserve doesn't decline on a straight line. It accelerates after 35, meaning the difference between 36 and 39 is bigger than the difference between 30 and 36. |
| Miscarriage risk (Factor 6) |
Under 35: ~10-15% | 35-39: ~20-25% | 40+: ~35-50% | Most early miscarriages happen because the embryo had the wrong number of chromosomes. It's the same driver as the egg quality decline — which means miscarriage risk and age track together for the same biological reason. |
| Cumulative time to pregnancy | Higher probability per cycle; more cycles available | Lower probability per cycle; timeline starts to compress | Each month matters more. The math works against you quickly. | Here's a number most people don't hear: the average time from starting fertility treatment to a live birth is about two years. That's not a worst case. That's the average, across 157,000 women. |
| Input | On track | Needs attention | Needs action | Notes |
|---|---|---|---|---|
| BMI | 18.5 - 24.9 | 25 - 29.9 (overweight) or 17 - 18.4 (underweight) | 30+ (obesity) or < 17 (can shut down ovulation) | This isn't about appearance. Fat tissue produces estrogen, and too much throws off the hormonal balance that controls ovulation. Too little body fat, and your brain decides conditions aren't safe enough to ovulate at all. |
| Marker | On track | Needs attention | Needs action | Notes |
|---|---|---|---|---|
| HbA1c | < 5.7% | 5.7 - 6.4% (prediabetic range) | > 6.4% | These aren't fertility-specific cutoffs, but here's why they matter: a prediabetic HbA1c carries a 48% chance of developing gestational diabetes. Worth knowing before you get pregnant, not after. |
| Fasting insulin | < 10 μIU/mL | 10 - 15 μIU/mL | > 15 μIU/mL | Your lab's "normal range" goes up to 20. But insulin resistance can silently affect your fertility well below that. Insulin can be elevated for years before your blood sugar catches up — by then, you've been losing time. |
| Marker | On track | Needs attention | Needs action | Notes |
|---|---|---|---|---|
| hs-CRP (high-sensitivity C-reactive protein) |
< 1.0 mg/L | 1.0 - 3.0 mg/L | > 3.0 mg/L | This is the simplest measure of systemic inflammation — the kind that runs quietly in the background. Chronic inflammation above 1.0 is associated with poorer implantation, higher pregnancy loss, and worse IVF outcomes. It's also one of the places where the insulin story, the weight story, and the autoimmune story all converge. A $15 blood test that almost nobody orders in a fertility workup. |
| Pathway | What happens | Notes | ||
|---|---|---|---|---|
| Hormonal disruption (HPA axis) |
Chronic stress activates the hypothalamic-pituitary-adrenal axis, increasing cortisol. Prolonged cortisol can disrupt hormone production, suppress ovulation, and reduce follicle maturation. | This is the pathway people mean when they say stress affects fertility. Chronic cortisol disrupts the hormones that trigger ovulation. The irony: "just relax" is terrible advice when you're doing something inherently stressful. | ||
| Endometrial impact (direct tissue effect) |
A 2026 study (Marti-Garcia et al., Scientific Reports) measured cortisol directly in endometrial tissue. Psychologically stressed patients had significantly elevated endometrial cortisol, which was associated with changes in 182 genes involved in implantation, immune response, and cell adhesion. Patients above a cortisol threshold had a 32% higher relative risk of not becoming pregnant. | One study, but striking: cortisol was measured directly in uterine tissue, not just blood. Stressed patients had changes in 182 genes involved in implantation. That's not a hormone signaling problem — that's stress physically remodeling the environment where an embryo would land. | ||
| Cortisol testing (4-point salivary or serum) |
Morning salivary cortisol: 0.2-0.7 μg/dL. Evening: < 0.1 μg/dL. Serum cortisol (AM): 6-20 μg/dL. The pattern matters more than any single number — cortisol should be highest upon waking and drop 75-80% by bedtime. A flattened or inverted curve suggests chronic stress or adrenal dysregulation. No universally standardized fertility-specific test exists; endometrial cortisol measurement (as in the study above) is research-only, not clinically available. | A single morning cortisol draw tells you almost nothing — it's a snapshot of a moving target. The 4-point salivary cortisol (morning, noon, evening, bedtime) gives you the curve, which is what matters. It's used in functional medicine but not mainstream fertility. If stress is clearly a factor in your life, this test can tell you whether it's showing up in your biology.Available through functional medicine practitioners. ~$100-200. Not standard in fertility clinics. | ||
| Input | On track | Needs attention | Needs action | Notes |
|---|---|---|---|---|
| Smoking | Non-smoker | Former smoker (some residual effect on reserve) | Current smoker | Smoking can move your menopause up by 1 to 4 years. If you'd naturally hit menopause at 50, smoking could effectively make your ovaries 46. It damages eggs, sperm DNA, implantation, and miscarriage risk all at once. No other lifestyle factor comes close. |
| Alcohol | None or minimal | Moderate | Heavy use | The evidence here is genuinely messier than for smoking. Light to moderate drinking doesn't show a clear fertility effect in most studies. Heavy drinking does. Less is better, but this isn't the factor where small changes will make or break your outcome. |
| Sleep | 7-9 hours, consistent schedule | Irregular sleep or < 7 hours | Shift work or chronic disruption | Your reproductive hormones follow a circadian rhythm. Shift work and chronic sleep disruption throw that rhythm off, which can affect ovulation timing and quality. Consistent sleep matters more than total hours. |
| Exposure | On track | Needs attention | Needs action | Notes |
|---|---|---|---|---|
| Heavy metals (lead, mercury, cadmium) |
Blood lead < 3.5 μg/dL Mercury < 5 μg/L Cadmium < 0.5 μg/L |
Above reference ranges | Significantly elevated | Lead and cadmium are associated with longer time to pregnancy, lower sperm quality, and increased miscarriage risk. Mercury accumulates from fish consumption and dental amalgams. The tricky part: you can have "low-level" exposure that's technically below toxicity thresholds but still enough to disrupt reproductive hormones. A blood or urine test can check. Most fertility clinics don't, but the exposure is more common than people realize. |
| BPA and phthalates (endocrine disruptors) |
Low exposure (glass/steel containers, fragrance-free products, minimal processed food packaging) | Moderate exposure (regular plastic food storage, conventional personal care products) | High exposure (heated plastics, heavy fragrance use, occupational exposure) | BPA and phthalates mimic estrogen and disrupt hormone signaling. Higher urinary BPA has been associated with fewer eggs retrieved, lower fertilization rates, and reduced embryo quality. Phthalates are linked to lower sperm quality and earlier ovarian aging. These are in plastics, receipts, fragrances, and food packaging. You can't eliminate exposure entirely, but reducing it is straightforward: don't heat food in plastic, switch to fragrance-free personal care, and filter your water. |
| Pesticides (organochlorines, organophosphates) |
Primarily organic produce, filtered water | Standard produce consumption, no specific avoidance | Occupational or high-volume agricultural exposure | A Harvard study following women through IVF found that those who ate the most high-pesticide-residue produce had 18% fewer eggs and 26% lower odds of a live birth compared to those who ate lower-residue produce. The practical move isn't all-or-nothing organic — it's focusing on the "Dirty Dozen" highest-residue foods and not worrying about the rest. |
| Nutrient | On track | Needs attention | Needs action | Notes |
|---|---|---|---|---|
| Vitamin D | > 30 ng/mL (some specialists target 40+) | 20 - 30 ng/mL (insufficient) | < 20 ng/mL (deficient) | About 40% of US adults are deficient. Higher pregnancy rates above 30 ng/mL. Toxicity is extremely rare at normal supplement doses.Just supplement. 2,000-4,000 IU/day, a few dollars/month. Test ($30-50) if you want to know where you stand. |
| Folate | RBC folate > 400 ng/mL (or serum folate > 20 ng/mL) | RBC folate 200 - 400 ng/mL | RBC folate < 200 ng/mL, or taking folic acid with a known MTHFR variant | Everyone knows folate prevents neural tube defects. Fewer people know the form matters. If you have an MTHFR variant (see Factor 4), standard folic acid may not convert efficiently. Methylfolate bypasses that step entirely.Your call. Switch to methylfolate prenatal (~$30-40/mo) or test MTHFR first (~$100-200, one time). See Factor 4 for the full tradeoff. |
| Homocysteine | < 10 μmol/L | 10 - 15 μmol/L | > 15 μmol/L | Think of this as a downstream signal. If your body isn't processing folate and B12 well, homocysteine rises. Elevated levels have been linked to recurrent pregnancy loss. If you're already taking methylfolate and B12 and it's still high, that's a sign something else is going on.Test it. $30-50 blood draw. Tells you if your methylation system is actually working. |
| CoQ10 | Supplementing (especially if 35+) | Not supplementing | N/A | Your eggs need enormous amounts of energy to divide correctly, and that energy comes from mitochondria. CoQ10 supports mitochondrial function, which declines with age. The biology makes sense; the clinical trial evidence is still catching up.Just take it. 200-600 mg/day ubiquinol. ~$20-40/mo. No meaningful side effects. No useful blood test. |
| Iron / Ferritin | Ferritin > 40 ng/mL | Ferritin 15 - 40 ng/mL ("normal" but not optimal) | Ferritin < 15 ng/mL or iron-deficiency anemia | Your doctor may say your iron is "fine" at a ferritin of 18. That's technically not anemic — but it's depleted. About 30% of reproductive-age women are iron-depleted without being anemic. Low ferritin affects egg quality, placental development, and energy. Too much iron is genuinely harmful — iron overload damages organs, and some people carry hemochromatosis variants that make this dangerous.Test first. Ferritin test is ~$20-30. Don't supplement blind — iron is one of the few nutrients where more is not always better. |
| B12 | > 400 pg/mL | 200 - 400 pg/mL | < 200 pg/mL | Low B12 feeds the same problem as MTHFR variants: poor methylation, rising homocysteine, impaired cell division. Especially common on plant-based diets or metformin (often prescribed for PCOS). Your lab's "normal" starts at 200, but symptoms can appear well above that.Just take it. Water-soluble — you pee out what you don't need. Cheap and safe. Essential if on metformin. |
| Zinc | > 80 μg/dL (serum) | 60 - 80 μg/dL | < 60 μg/dL | Zinc is involved in egg maturation, fertilization, and early embryo development — and it's critical for sperm production. One of the most commonly deficient minerals worldwide. Overdoing it long-term (50+ mg/day) can deplete copper, so don't mega-dose.Check your prenatal — most include 15-30 mg, which is enough. If not, a standalone supplement is a few dollars/month. |
| Omega-3 index | > 8% | 4 - 8% | < 4% | Omega-3s reduce systemic inflammation, which affects implantation and pregnancy maintenance. Most Americans are well below optimal levels. Well-studied in pregnancy. Look for third-party tested brands to avoid mercury and oxidation.Just take it. Quality fish oil or algae-based DHA, 1-2g/day. ~$15-30/mo. Safe in pregnancy. |
The Six Things That Have to Work
| Marker | On track | Needs attention | Needs action | Notes |
|---|---|---|---|---|
| AMH (ovarian reserve) |
See age chart below | See age chart below | See age chart below | A single cutoff doesn't work for AMH. An AMH of 1.5 at 30 is low; the same number at 40 is solid. Always interpret relative to your age. |
| FSH (Day 3) |
< 10 IU/L | 10 - 15 IU/L | > 15 IU/L | FSH fluctuates from cycle to cycle, so one high reading isn't a diagnosis — but it's not nothing, either. The important thing: FSH only means something when you read it next to estradiol. High E2 on Day 3 artificially suppresses FSH, which can make your numbers look reassuring when they're not. |
| Estradiol (E2) (Day 3) |
< 80 pg/mL | 80 - 100 pg/mL | > 100 pg/mL | This is the sneaky one. High estradiol on Day 3 suppresses FSH, making your reserve look better than it is. If your doctor says your FSH is "normal" but didn't check estradiol at the same time, that "normal" may be a false reassurance. |
| Antral follicle count (AFC, via ultrasound) |
15+ | 6 - 14 | < 6 | This is the physical headcount — how many follicles are visible on ultrasound early in your cycle. Combined with AMH, it gives the most complete picture of what your ovaries have to work with. Neither number alone tells the full story. |
| Fragile X premutation (FMR1 gene test) |
Negative | Family history of early menopause but untested | Premutation carrier | One in 250 women carries this premutation without knowing it. Of those, 20% will experience premature ovarian insufficiency — compared to 1% of the general population. If anyone in your family went through early menopause, this is worth ruling out. |
| DHEA-S (adrenal/ovarian precursor) |
180 - 400 μg/dL (age-dependent) | 100 - 180 μg/dL | < 100 μg/dL (especially if 37+ with low reserve) | DHEA is a precursor hormone your ovaries use to make the androgens that feed egg development. It declines naturally with age — by 40, you have about half what you had at 25. There's real evidence that supplementing DHEA improves egg yield and quality in diminished ovarian reserve. But if your androgens are already elevated (PCOS), supplementing makes things worse — more acne, hair growth, further disruption.Test first. $30-50 blood draw. Don't supplement without checking — DHEA can help or hurt depending on where you start. |
| Age | Solid for age | Lower than expected | Low / diminished reserve |
|---|---|---|---|
| Under 30 | > 2.5 ng/mL | 1.5 - 2.5 ng/mL | < 1.5 ng/mL |
| 30-34 | > 2.0 ng/mL | 1.2 - 2.0 ng/mL | < 1.2 ng/mL |
| 35-37 | > 1.5 ng/mL | 1.0 - 1.5 ng/mL | < 1.0 ng/mL |
| 38-40 | > 1.0 ng/mL | 0.5 - 1.0 ng/mL | < 0.5 ng/mL |
| 41+ | > 0.5 ng/mL | 0.2 - 0.5 ng/mL | < 0.2 ng/mL |
Based on population studies (22,920 women, 2025 nomogram; Cleveland Clinic; POSEIDON criteria). AMH below 1.2 ng/mL is classified as diminished ovarian reserve at any age. Values above that threshold still need to be interpreted relative to age.
| Marker | On track | Needs attention | Needs action | Notes |
|---|---|---|---|---|
| Concentration | > 15 million/mL | 5 - 15 million/mL | < 5 million/mL | These thresholds are floors, not targets. Meeting the minimum doesn't mean everything is fine — it means you're above the line where problems are almost certain. Most couples conceiving naturally have counts well above 15 million. |
| Total motility | > 40% | 20 - 40% | < 20% | Motility is about whether sperm are moving at all. It matters, but what matters more is progressive motility — whether they're actually swimming forward, not just vibrating in place. |
| Progressive motility | > 32% | 15 - 32% | < 15% | This is the one that matters most for natural conception. Sperm that move but don't go anywhere aren't going to reach the egg. If you only focus on one motility number, make it this one. |
| Morphology (normal forms) |
> 4% | 2 - 4% | < 2% | 4% normal sounds terrible until you learn it's the standard threshold. Most men have the vast majority of sperm looking "abnormal" under a microscope. Morphology alone is a weak predictor of fertility — don't let this number panic you if everything else looks fine. |
| DNA fragmentation (DFI) |
< 15% | 15 - 30% | > 30% | This is the test that often explains "unexplained" infertility. It's not included in a standard semen analysis — you have to specifically ask for it. About 1 in 9 men with perfectly normal count, motility, and morphology still have high DNA fragmentation. That hidden damage affects whether embryos develop and whether pregnancies hold. |
| Oxidative stress (ROS / MiOXSYS) |
sORP < 1.36 mV | sORP 1.36 - 1.70 mV | sORP > 1.70 mV | Here's an underappreciated connection: high oxidative stress is one of the main causes of DNA fragmentation. If DFI comes back elevated and you want to know why — or if you want to track whether lifestyle changes and antioxidants are actually working — ROS testing gives you a mechanism, not just a result. It's not first-line, but it turns "your DNA fragmentation is high" into something you can act on. |
| Male hormones (testosterone, FSH, LH) |
Testosterone 300-1,000 ng/dL FSH 1.5-12.4 mIU/mL LH 1.8-8.6 mIU/mL |
Testosterone 200-300 ng/dL, or FSH/LH borderline | Testosterone < 200 ng/dL, or FSH > 20 mIU/mL (suggests testicular failure) | If sperm count is very low, the question is why. Hormones help distinguish whether the issue is production (the factory isn't making sperm) or plumbing (sperm are being made but can't get out). Different causes, completely different treatments. |
| Sperm aneuploidy (FISH testing) |
< 1% aneuploidy per chromosome probe; < 5% total | 1-3% per probe or 5-10% total | > 3% per probe or > 10% total | Not a first-line test — it's expensive and specialized. But if you're dealing with recurrent loss, repeated failed fertilization, or severe male factor, this can reveal whether the sperm themselves are carrying chromosomal problems. Sometimes the answer isn't the egg. |
11% of men with completely normal count, motility, and morphology still have high DNA fragmentation. A standard semen analysis alone can miss real problems.
| Marker | On track | Needs attention | Needs action | Notes |
|---|---|---|---|---|
| Tubal patency (HSG or HyCoSy) |
Both tubes open | One tube open, one questionable | One or both blocked, or hydrosalpinx | A quarter to a third of female infertility involves blocked or damaged tubes. The less obvious part: a hydrosalpinx (fluid-filled tube) doesn't just block the path — it can leak toxic fluid back into the uterus and impair implantation even if you bypass the tubes entirely. |
| Ovulation | Confirmed by ultrasound + timed bloodwork | Assumed from regular cycles, but unconfirmed | Anovulatory | Regular periods don't confirm ovulation. Up to 10% of women with regular cycles have anovulatory cycles. PCOS and hypothalamic amenorrhea are the most common causes. |
| Testosterone (total and free) |
Total: 15 - 46 ng/dL Free: 0.5 - 3.5 pg/mL |
Mildly elevated (suggestive of PCOS or adrenal contribution) | Significantly elevated or very low | The framework mentions PCOS in the ovulation row, but this is the marker that actually identifies it. Elevated free testosterone is the hormonal signature of PCOS — and you can have PCOS with regular periods if testosterone is high enough to impair egg quality without fully stopping ovulation. Very low testosterone can also be a signal of diminished ovarian function. |
| SHBG (sex hormone binding globulin) |
40 - 120 nmol/L | < 40 nmol/L | < 25 nmol/L | SHBG is the protein that binds testosterone and controls how much is "free" and active. Low SHBG means more free testosterone circulating, even if your total testosterone looks normal. Insulin resistance drives SHBG down — so this is where the blood sugar story and the PCOS story connect. If SHBG is low, look at fasting insulin. |
| Cycle monitoring (serial tracking) |
Monitored: follicle tracking, timed hormone draws, confirmed ovulation and luteal support | Partial: Day 3 labs only, or a single untimed progesterone draw | None: no imaging or cycle-timed bloodwork | A "Day 21 progesterone" is only meaningful if you ovulated around Day 14. If your cycle is 33 days, Day 21 is too early and the result is meaningless. Most OB workups only do the Day 3 panel and stop. |
| Marker | On track | Needs attention | Needs action | Notes |
|---|---|---|---|---|
| Aneuploidy risk (chromosomal abnormality) |
Under 35: ~35% abnormal | 35-39: ~50% abnormal | 40+: ~60-80% abnormal, climbing steeply after 42 | This is the same story as the Age input above, but here's why it shows up again: age tells you the probability, but aneuploidy is the mechanism. You can't change the rate, but understanding it changes your decisions — how many eggs to bank, whether PGT-A testing is worth it, how aggressively to move. |
| Carrier screening (both partners) |
No shared carrier status | One partner is a carrier (not harmful alone, but both need to be tested) | Both partners carry the same condition (1 in 4 chance of affected embryo) | About 1 in 4 people is a carrier for at least one genetic condition. Most don't know until it affects a pregnancy. Simple blood test for both partners. |
| Karyotype (chromosomal structure, both partners) |
Normal | Variant of uncertain significance | Balanced translocation found | Balanced translocations are carried silently. The carrier is healthy, but many of their embryos won't be viable. Often only discovered after recurrent loss. |
| MTHFR variants (C677T, A1298C) |
No variants, or heterozygous with normal homocysteine | Heterozygous (one copy) for C677T or A1298C | Homozygous C677T or compound heterozygous (one of each) | MTHFR affects your body's ability to convert folic acid into its usable form. If you have a variant, standard prenatal vitamins may not be giving you what you need. You can have normal homocysteine and still not be getting adequate active folate to developing tissue. Methylfolate is safe for most people, but it can cause anxiety, irritability, or insomnia in some (particularly fast COMT metabolizers).Your call. Methylfolate prenatal (~$30-40/mo) or test MTHFR first (~$100-200, one time). If methylfolate makes you jittery, test — you may not need it. |
| Sperm DNA integrity | DFI < 15% | DFI 15-30% | DFI > 30% | This is the same test from Factor 2 (Sperm), but it shows up here because the consequences land here. High DFI doesn't just mean fewer fertilizations — it means more embryos that start developing and then stop, or pregnancies that implant and then fail. If you've already tested DFI, you have this number. If you haven't, see Factor 2. |
By the early 40s, 60-80% of embryos will have chromosomal abnormalities, and the rate climbs steeply after 42. This is the single biggest reason fertility declines with age. It's not about how many eggs you have. It's about how many are viable.
| Marker | On track | Needs attention | Needs action | Notes |
|---|---|---|---|---|
| Lining thickness | > 8 mm, trilaminar | 7 - 8 mm | < 7 mm | Thickness gets all the attention, but the pattern matters just as much. A trilaminar (three-layer) pattern suggests the lining is responding well to estrogen. A thick lining that's homogeneous may actually be less receptive than a thinner one with the right structure. |
| Cavity shape (hysteroscopy / SIS) |
Clear, no abnormalities | Small irregularity, monitoring | Polyps, fibroids, septum, Asherman's | Polyps and small fibroids are extremely common — most women over 35 have at least one. The question isn't whether they exist, but whether they're in a location that interferes with implantation. A hysteroscopy can both find them and remove them in the same procedure. |
| Adenomyosis (MRI is gold standard) |
No evidence | Suspected based on symptoms or ultrasound | Confirmed | One of the most underdiagnosed conditions in fertility. It's like endometriosis, but inside the uterine wall instead of outside the uterus. Standard ultrasound often misses it. MRI is much better. If you have heavy, painful periods and nobody's mentioned this, it's worth asking about. |
| Endometriosis | No evidence / treated | Suspected (pain, history) but not confirmed | Active, untreated | One in ten women has endometriosis, but here's the catch: it can be completely silent. No pain, no heavy periods, no obvious symptoms. It can quietly degrade egg quality, damage tubes, and impair implantation — all while your standard workup comes back "normal." |
| Silent endometriosis (BCL6 / ReceptivaDx) |
Negative | Risk factors present but biopsy not done | Positive | This is how you find endometriosis that isn't visible on imaging or even during surgery. BCL6 is a protein marker in the uterine lining. In one dataset, over half of women with "unexplained" infertility tested positive. It's a simple endometrial biopsy, not an operating room procedure. |
| Endometritis (chronic uterine infection) |
Negative (CD138 biopsy) | Prior infection treated, not re-confirmed | Chronic endometritis found | Chronic endometritis is a low-grade uterine infection with no obvious symptoms. It's detected by biopsy, not culture. The tricky part: labs don't agree on exactly how many inflammatory cells count as positive. The good news: when it's found, a course of antibiotics usually resolves it. |
| Uterine microbiome | Lactobacillus ≥ 90%, Bifidobacterium ~10%, opportunistic pathogens < 1%, no strict pathogens | Lactobacillus 50-90%, mild imbalance | Lactobacillus < 50% or pathogen-dominant (dysbiosis) | Your uterus isn't sterile — it has its own microbiome. When it's dominated by Lactobacillus (≥90%), implantation rates are dramatically higher. In one study, live birth rates were 59% with a Lactobacillus-dominant uterus vs. 7% without. This testing isn't mainstream in the US yet, but some international clinics already treat it as standard. |
| IgA Secretora (endometrial immune marker) |
300 - 2,500 ng/mL | Below 300 ng/mL | Very low (suggests reduced local immunity or possible congenital deficit) | If the uterine microbiome is the ecosystem, IgA is the immune system that polices it. Low IgA may explain why some women get recurrent endometritis even after antibiotics clear it — the local immune defense can't keep infections from coming back. Tested in some international clinics alongside the microbiome panel. Not standalone useful, but if you're seeing repeated infections or dysbiosis, this is a missing piece. |
| NK cell subtypes (endometrial biopsy, not blood) |
Balanced ratio: majority angiogenic (CD16-, ~70-80%), minority cytotoxic (CD16+, ~20-30%) | Ratio shifting toward cytotoxic | Predominantly cytotoxic NK cells (CD16+ > 50%) with low or absent angiogenic NK cells (CD16-) | Here's why this topic is so confusing: when US doctors say "NK cell testing doesn't work," they're talking about counting NK cells in your blood. And they're right — that test tells you almost nothing about your uterus. But endometrial NK subtyping is a completely different test. It looks at the NK cells actually in your uterine lining and distinguishes between the helpful ones (CD16-, which build blood vessels for implantation) and the harmful ones (CD16+, which can attack). It's the ratio that matters, not the total number. This requires an endometrial biopsy, not a blood draw. |
| Implantation window (ERA test) |
Receptive at expected timing | Borderline / unclear result | Displaced | This test has been marketed heavily, but the data hasn't kept up with the hype. A large reanalysis found that personalized transfer timing based on ERA didn't actually improve live birth rates. If someone recommends it, understand what it costs versus what the evidence says it delivers. |
Most of these markers are not part of a standard fertility workup. They're typically only investigated after a failed pregnancy or transfer. Some (adenomyosis, BCL6, endometritis) have strong evidence but are routinely overlooked. Others (microbiome, NK subtypes, ERA) have varying levels of evidence, but the quality of the testing matters: an endometrial NK subtype analysis from a biopsy is a fundamentally different test from a peripheral blood NK count, even though both get called "NK cell testing."
| Marker | On track | Needs attention | Needs action | Notes |
|---|---|---|---|---|
| TSH (thyroid function) |
1.0 - 2.5 mIU/L | 2.5 - 4.0 mIU/L | > 4.0 mIU/L | Here's a common disconnect: your OB may say your thyroid is "normal" at 4.0. A reproductive endocrinologist would want it under 2.5. They're using different cutoffs for different purposes. For fertility, the tighter range matters — and it's easily treatable with medication. |
| Thyroid antibodies (TPO, thyroglobulin) |
Negative | Low-positive (monitoring recommended) | Positive | This is the test most often skipped. You can have a perfectly normal TSH and still have positive thyroid antibodies — and those antibodies alone raise miscarriage risk. The uncomfortable part: we know the antibodies increase risk, but we're less certain that treating with thyroid medication fixes it when TSH is already normal. The risk is real; the solution is still being figured out. |
| Prolactin | < 25 ng/mL | 25 - 50 ng/mL | > 50 ng/mL | Elevated prolactin quietly shuts down ovulation. The causes are usually identifiable — stress, medication, or a small benign growth on the pituitary — and it responds well to treatment. Worth checking if your cycles are irregular or absent. |
| Progesterone support (luteal phase) |
Adequate (confirmed 7 days post-ovulation) | Tested but not timed to actual ovulation | Low / luteal phase defect | Timing matters more than the number. A progesterone drawn on "Day 21" of a 35-day cycle is meaningless — you probably hadn't ovulated yet. It needs to be drawn 7 days after confirmed ovulation. If nobody tracked when you ovulated, the number on the lab report is just noise. |
| Coagulation panel (Protein S, C, antithrombin, Factor V Leiden) |
Protein S: 60-150% Protein C: 70-140% Antithrombin: 80-120% Factor V Leiden: negative |
Borderline low on any marker | Deficiency confirmed, or Factor V Leiden positive (heterozygous or homozygous) | The pattern in fertility care is maddening: these are only ordered after two or three pregnancy losses. Every single test is a simple blood draw that could have been done from the start. If a clotting disorder is found, it's treatable with blood thinners during pregnancy. |
| Antiphospholipid antibodies | Negative | Low-positive (needs repeat to confirm) | Confirmed positive | One of the most well-established causes of recurrent pregnancy loss, and it's treatable. The catch: it has to be confirmed by two positive tests, 12 weeks apart — a single positive isn't a diagnosis. If you've had multiple losses, this should be on the list. |
| Celiac panel | Negative | Borderline / weak positive | Positive | Silent celiac — no obvious GI symptoms — is an underrecognized cause of infertility and recurrent loss. Maybe 1-3% of women with unexplained infertility have it. The remarkable part: fertility typically returns to normal with dietary changes alone. It's a blood test. |
| Immunoglobulin levels (IgG, IgA, IgM) |
IgG: 700-1,600 mg/dL IgA: 70-400 mg/dL IgM: 40-230 mg/dL |
Below lower limits on any marker | Significantly low (may indicate immunodeficiency) | Think of this as the immune system's overall capacity. If someone has recurrent losses and normal clotting, normal thyroid, normal karyotype — and their doctors are running out of explanations — low immunoglobulins can point toward an immune system that doesn't mount the right response to pregnancy. It's a second-tier investigation, not a starting point. But for the truly unexplained cases, it's one of the things that can break the "we don't know why" cycle. |
Coagulation panels, thyroid antibodies, and celiac screening are typically only ordered after 2-3 pregnancy losses. Every one of them is a simple blood test that can be done at any time.
Sources and evidence notes: AMH age-adjusted ranges: population-based nomogram study (22,920 women, 2025); Cleveland Clinic; POSEIDON criteria. FSH/E2 Day 3: ASRM guidelines. Fragile X/POI: ACOG Committee Opinion; NICHD. DHEA-S and diminished ovarian reserve: DOST trial; multiple clinical studies. Sperm parameters: WHO 6th Edition (2021). DFI thresholds and 11% stat: multiple studies including Belloc et al. 2014. ROS: technically validated but not recommended for routine clinical use per WHO 2021. Male hormones: AUA/ASRM guidelines. Sperm FISH: validated, indicated for severe male factor/RPL. Tubal factor prevalence: ASRM. Testosterone/SHBG: Endocrine Society; Rotterdam criteria for PCOS. Adenomyosis: Fertility & Sterility 2020 meta-analysis. BCL6/ReceptivaDx: 96% PPV in their published data; growing adoption but not universally standard. CD138 endometritis: standard method, no agreed diagnostic threshold. Uterine microbiome: strong mechanistic evidence (Microbiome journal 2021), no clinical guidelines for testing/treatment. NK cells: mainstream guidelines (ASRM, ESHRE) do not recommend peripheral blood testing; endometrial subtyping is a different test. ERA: recent reanalysis suggests no improvement in live birth rates; ESHRE 2024 recommends against routine use. TSH: ASRM 2024. Thyroid antibodies: meta-analysis of 22 studies. hs-CRP: AHA/CDC cardiovascular thresholds applied to reproductive outcomes; multiple IVF outcome studies. HbA1c: ADA thresholds (not fertility-specific). Fasting insulin: optimized thresholds (normal lab range 2-20). Ferritin: functional medicine thresholds > 40 ng/mL; WHO iron deficiency criteria. B12: functional thresholds > 400 pg/mL. Zinc: WHO; multiple fertility studies. Omega-3 index: Harris & von Schacky framework. CoQ10: biological rationale strong, no definitive large RCT. Smoking: ASRM 2023. Environmental toxins: ESHRE/ASRM committee opinions on environmental exposures; Harvard EARTH study (pesticides and IVF outcomes). Celiac: ESHRE recommends screening. Stress/endometrial cortisol: Marti-Garcia et al., Scientific Reports 2026 (n=84). All ranges are approximate and should be interpreted by a reproductive endocrinologist in the context of your full clinical picture.