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What is an embryo transfer? 

An embryo transfer is the process that occurs in the last step of IVF, during which an embryo is transferred into the uterus with the aim of achieving a pregnancy.i There are two different protocols: fresh and frozen.

  • Fresh embryo transfer: The embryo is transferred from the culture dish into the uterus three to five days following an egg retrieval.
  • Frozen embryo transfer (FET): Embryos from a previous egg retrieval cycle were cryopreserved (frozen) for future use; now, one or more embryos are thawed and transferred to the uterus.ii
IVF cycle
The primary steps of IVF for a fresh embryo transfer

Fresh embryo transfer is usually done on either Day 3 or Day 5 following egg retrieval and fertilization. On Day 3, an embryo is in the cleavage stage and called a cleavage-stage embryo. It has approximately eight cells in total. On Day 5, the embryo should be at the blastocyst stage and is more developed.iii

Importantly, embryo transfer is not the same as implantation. While embryo transfer describes the process of transferring the embryo into the uterus, embryo implantation occurs when the developing embryo attaches to the uterine lining, which is what establishes a pregnancy.iv

What is the embryo transfer process?

The process for a fresh embryo transfer differs from a FET when it comes to the monitoring and drugs that may be used to support the body.

Fresh embryo transfer

Following ovarian stimulation, eggs are retrieved and fertilized in vitro to create embryos. The embryos will be cultured, usually for three to five days, and then one or more embryos will be transferred into the uterus. Any remaining embryos can be vitrified (frozen) for future FET.

After the egg retrieval, the patient typically will be instructed to take estrogen (vaginally, orally, or transdermally) and progesterone (vaginally or via injection) to support the lining of the uterus, also called the endometrium.v Once the endometrium is ready, an embryo that is developing in the lab is transferred directly into the uterus on Day 3 or Day 5 of embryo growth (i.e., three or five days after the egg retrieval). The patient will typically continue progesterone and estrogen at a minimum until the day of a pregnancy test, which is about eight to 12 days after transfer.vi,vii

Frozen embryo transfer (FET)

Typically, a patient will do either a natural (or modified natural) cycle or a medicated cycle.

Natural and modified natural cycle for FET

This protocol works best in patients with a regular menstrual cycle, since the embryo transfer day is based on the timing of their natural cycle. Because fewer or no medications are used, it is often considered more patient-friendly and may have lower costs. The protocol involves regular transvaginal ultrasounds to check the thickness of the endometrium, and regular monitoring of hormones in the blood — namely estrogen, progesterone and luteinizing hormone (LH) to track ovulation.

Tracking the day of ovulation is important because embryo transfer occurs a specific number of days after ovulation (typically five to six days after blood samples show LH surge for a blastocyst transfer).viii

In modified natural cycles, ovulation will be triggered with an injection of human chorionic gonadotropin (hCG) when a dominant ovarian follicle reaches approximately 16 to 20 mm in diameter.ix This trigger helps narrow down the timing of the transfer since the transfer will usually occur six to seven days after hCG trigger injection.x

In a natural or modified natural cycle, the patient’s corpus luteum (a structure in the ovaries comprised of follicle cells that are modified after ovulation) produces adequate progesterone to support implantation. However, typically luteal phase support (e.g., progesterone medication) will still be prescribed.

Although less common, some patients may take mild ovarian stimulation medication that is similar to stim meds used to help grow multiple follicles for IUI or egg retrieval (e.g., Letrozole®).xi This medication can increase the number of follicles a patient ovulates, which is believed to potentially improve endometrial lining thickness and/or receptivity, as well as strengthen the luteal phase through multiple corpus lutea. However, due to overall shortage of clinical evidence, it remains unclear as to whether this medication improves live birth rates in individuals with regular menstrual cycles.  

Medicated cycle for FET

Medicated frozen embryo transfers are also known as hormone replacement, artificial, or programmed FET cycles. Medicated FET cycles are more common than natural FETs. They involve taking hormone medications such as estrogen and progesterone, which control the hormone levels in a cycle, therefore allowing for predictability.

Medicated FETs begin with daily estrogen supplementation starting on cycle days one to three. The estrogen supplements will suppress natural follicle development and ovulation. Once the endometrial lining is optimal, progesterone is started prior to embryo transfer.xii Typically, progesterone is taken for three days prior to a Day 3 embryo transfer and five days prior to a blastocyst transfer. It is often taken as progesterone in oil (PIO) injections or a combination of injections and vaginal suppositories.xiii,xiv

What tests are done before the transfer protocol?

To heighten the probability of embryo implantation after transfer, several tests will be done before and during the transfer protocol. These tests assess everything from the hormone levels in the blood to the size of follicles and the thickness of the uterine lining.

Blood testing is completed prior to embryo transfer, since ensuring optimal hormonal range is important to successful implantation (described below). An ultrasound will also be completed prior to transfer to assess endometrial thickness and endometrial pattern. The results help predict if the endometrium will be receptive for implantation.xv Sometimes, an extra ultrasound will be performed the day before embryo transfer to ensure that compaction of the uterine lining has occurred.xvi

Blood monitoring

Several hormones will be monitored via bloodwork prior to an embryo transfer.

Progesterone

The level of progesterone in the blood (P4) is measured prior to embryo transfer. For fresh embryo transfer, blood progesterone (P4) levels may be measured even before egg retrieval — typically the day of hCG trigger. At this point, it is desirable to have very low progesterone levels; if elevated, the development of the endometrium may not be synchronized with the development of the embryo.xvii In cases where progesterone levels are prematurely elevated (i.e., above 1.5 ng/mL) on the day of trigger, a decision to freeze the embryo(s) instead of transferring fresh could be made.xviii,xix,xx Premature luteinization has been estimated to occur in 12.3 to 46.7 percent of fresh IVF cycles. However, recent studies have addressed methods to prevent its occurrence via gonadotropin-releasing hormone (GnRH) agonist or antagonist protocols.xxi

By the time of fresh or frozen transfer, progesterone levels will be increased. Some studies suggest that blood progesterone level should be above 10 ng/mL directly before the transfer to support implantation.xxii,xxiii Physicians will often use a combination of published data, internal clinic data, and individualized recommendations to determine optimal progesterone ranges at the time of transfer.

It should also be noted that significantly elevated progesterone at transfer could potentially have a negative impact, too. One study by Kofinas et al. (2015) observed an ongoing pregnancy rate of 70 percent for P4 at 10 to 15 ng/mL vs. 33 percent for P4 higher than 40 ng/mL on the day of transfer.xxiv However, not all studies have observed this same trend for elevated P4 levels.xxv Note that these data refer to progesterone levels at the time of transfer, which will be lower than P4 bloodwork at the time of beta-hCG.

Estrogen

Blood estrogen level is also measured prior to embryo transfer. A study by Diluigi et al. (2005) found that a higher estrogen level is associated with better odds of implantation and pregnancy.xxvi They found that the odds pf pregnancy increased as levels of serum estrogen increased. A 2020 study showed that measuring estrogen and progesterone the day prior to embryo transfer improved live birth rates because cycles with imbalanced hormones prior to FET were rescheduled.xxvii

Thyroid hormone

Thyroid hormone levels are often monitored during IVF, as thyroid stimulating hormone (TSH) may increase during controlled ovarian stimulation (COS).xxviii During IVF and ovarian stimulation, the levels of serum estrogen are much higher than normal which puts stress on the thyroid gland and can cause TSH levels to rise. Because normal thyroid function is important for the health of a pregnancy, TSH levels are often monitored to ensure that they are within the normal range.xxix

Lining measurement

Prior to embryo transfer, endometrial thickness will be measured through an ultrasound to ensure that the endometrium is adequately prepared for the embryo to implant. A meta-analysis that included 88,056 IVF cycles found that a thinner endometrium is associated with lower pregnancy rates, decreased implantation rates, and lower live births.xxx

The endometrial pattern may also be an important consideration in embryo transfer. The endometrial pattern describes the anatomic appearance on ultrasound of the endometrium, which changes throughout the menstrual cycle in response to estrogen and progesterone. A pattern of three lines, known as a trilaminar pattern, is favorable just prior to starting progesterone supplementation.xxxi

What is the success rate of embryo transfers?

The success rates of each embryo transfer varies based on factors that include age, whether preimplantation genetic testing is completed, the patient’s medical conditions, the indication for IVF, and the transfer protocol used. The success rates relative to these various factors are discussed below.xxxii,xxxiii,xxxiv,xxxv

Age

As females age, there is an increase in genetic abnormalities within the egg, which contributes to a decline in pregnancy rates. A study by Yan et al. (2012) evaluated the success of embryo transfer of non-PGT tested embryos in 11,830 transfer cycles in different age categories.xxxvi They found that the pregnancy rate was highest in the 21 to 30 age group (60 percent) and lowest in the over 41 age group (27 percent). The pregnancy rate was 57 percent in patients aged 31 to 35 and 47 percent in patients aged 36 to 40. They also found that the rate of miscarriage was lowest in the 21 to 30 age category (9 percent), and highest in the over 41 age category (36 percent).

Based on a study by Cheung et al. (2021), the usage of donor eggs may mitigate this decrease in success rate of embryo transfer, since the average age of egg donors is younger.xxxvii This study of 1,080 cycles found no significant difference in the rate of pregnancy and live births in four groups of patients categorized by age (under 40, 40 to 44, 45 to 49, and 50 years old and up). They did, however, note a higher rate of first trimester pregnancy loss in patients 50 years old and up (20 percent).

Genetically tested embryos

Preimplantation genetic testing (PGT) is a technique used to genetically screen embryos in IVF to select which embryo(s) to transfer.xxxviii Research has shown that PGT-A, a form of PGT that screens for an abnormal number of chromosomes (aneuploidy), may help reduce the total number of embryo transfers, promote single embryo transfers, and reduce the rate of miscarriage during IVF, by selecting only euploid (chromosomally normal) embryos to transfer.xxxix,xl

Studies have suggested that PGT-A may improve outcomes in IVF patients — namely the success rate per transfer (not overall success rate of the cycle).xli,xlii One recent study by Sato et al. (2019) found that the use of PGT-A improved the live birth rate per transfer in patients with recurrent implantation failure to 63 percent compared to 32 percent.xliii

It is important to note whether studies are looking at improved success rates “per transfer” versus “cumulative live birth rates.” A recent large prospective randomized controlled trial showed that cumulative live birth rates were slightly lower in the PGT-A group (77 percent) than in the untested group (82 percent).xliv Other studies have similarly noted that PGT-A does not always provide a benefit, particularly for patients producing fewer than four embryos per cycle, due to having no euploid embryos to transfer or the potential harm of performing a biopsy on the embryo.xlv,xlvi,xlvii Note: PGT requires freezing of embryos, so all transfers will be FETs.

Frozen embryo transfer timeline when preimplantation genetic testing is used
The primary steps of IVF for a frozen embryo transfer, including PGT

Are fresh vs. frozen transfers more successful?

While studies examining fresh vs. frozen embryo transfer success rates do not consistently agree, the general consensus is that there are no differences in success rates for fresh vs. frozen transfer (in females who respond normally to IVF stimulation).

A meta-analysis of several studies by Wong et al. (2017) found no significant difference in the cumulative live birth rate between females who underwent fresh embryo transfer compared to frozen embryo transfer.xlviii They found that the live birth rate for fresh embryo transfer was 58 percent compared to a live birth rate of 56 to 65 percent for frozen embryo transfer.

A study by Boynukalin et al. (2020) analyzed the live birth rate in 2,523 Day 5 embryo transfers. They found that success rates comparing fresh vs. frozen transfers depended on the number of eggs retrieved.xlix They found that in patients with 11 to 25 eggs retrieved, the live birth rate was significantly higher in frozen embryo transfers compared to fresh embryo transfers. There was no significant difference in fresh vs. frozen embryo transfers in patients with one to 10 eggs retrieved. Because pregnancy can worsen ovarian hyperstimulation syndrome (OHSS), fresh embryo transfer should be avoided in patients at a high risk of OHSS (i.e., high estradiol levels during IVF, high number of follicles).

There is conflicting data on the impact of fresh vs. frozen embryo transfers on obstetric and perinatal outcomes. A large study by Ernstad et al. (2019) identified possible risks associated with frozen embryo transfer.l They found that frozen embryo transfer is associated with higher risks of postpartum hemorrhage, delivery after full term (post-term birth), macrosomia (larger baby), and hypertensive disorders of pregnancy. There is currently a multi-center randomized clinical trial to investigate the impact of medications used for FET on risk of preeclampsia during pregnancy.li

In contrast, a sibling study studying the effects of fresh vs. frozen embryo transfer did not find any differences in obstetric or perinatal outcomes.lii Data was collected from pregnancies resulting from a fresh transfer and matched to a pregnancy from a frozen transfer to the same individual.

Day 3 (D3) vs. Day 5 (D5) embryos

In general, transferring Day 5 blastocyst embryos is believed to have a better chance of success than Day 3 cleavage-stage embryos. Some embryos arrest (stop developing) between Day 3 and Day 5. By waiting until day 5, the embryologist will know which ones did not make it, thereby avoiding the transfer of those embryos. On Day 3, it is difficult to predict which embryos will make it to the blastocyst stage.

A Cochrane review of 4,031 couples showed that pregnancy and live birth rates were higher in Day 5 embryo transfers compared to Day 3 in the case of fresh embryo transfers.liii Their evidence suggests that if 29 percent of patients had a live birth following a Day 3 transfer, 32 to 42 percent would have a live birth following a Day 5 transfer.

In contrast, a smaller study of 190 females who underwent intracytoplasmic sperm injection (ICSI) during IVF found that the success rate of fresh embryo transfers was similar between Day 3 and Day 5 embryos.liv The implantation rate was 47 percent for Day 3 embryos, and 45 percent for Day 5 embryos. The live birth rate for Day 3 transfers was 37 percent, compared to 35 percent for Day 5 transfers.

What drugs are used for an embryo transfer?

There are multiple medications that are routinely used in embryo transfers, and it depends on the protocol. Each drug given is meant to support some biological function that would increase the chance of successful implantation of the embryo(s).

Medications that prepare the endometrium

Estradiol is the active form of estrogen and can be given as an oral tablet (Estrace ®) or a transdermal patch. It usually starts on day one to three of the natural period in a FET and after retrieval in a fresh transfer. Estradiol is continued until the day of the pregnancy test following embryo transfer or until 10 to 12 weeks’ gestation if pregnant. Estradiol works to prime the endometrium and suppresses the natural growth of ovarian follicles. It also suppresses ovulation in FETs.lv

Progesterone usually starts the day after egg retrieval in a fresh cycle. It is an important hormone that facilitates implantation and helps maintain a pregnancy once it is established. It is commonly continued to 10 to 12 week’s gestation.lvi In a FET, progesterone is usually started three to five days before transfer, once the uterine lining has reached an appropriate thickness and patterning.

Trigger shots

Not all transfer protocols will involve a trigger shot. In fresh transfers, or in modified natural FET cycles, a trigger shot will be needed to trigger ovulation. Most FETs do not involve a trigger shot.

Physiologically, ovulation is caused by a surge in luteinizing hormone (LH). Injectable hCG triggers (e.g., Ovidrel®, Novarel®, or Pregnyl®) function in a manner similar to LH: the hCG is injected and will trigger ovulation because it mimics LH.

Fresh transfers often involve using an hCG trigger prior to egg retrieval. For modified natural frozen embryo transfer, ovulation is typically triggered with an hCG trigger shot when a dominant ovarian follicle reaches approximately 16 to 20 mm in diameter. The trigger helps narrow down the timing of transfer (as opposed to being used to release follicles).

A GnRH agonist can also be used to trigger ovulation in antagonist IVF cycles. This type of trigger is particularly common when there is a risk of ovarian hyperstimulation syndrome (OHSS).lvii GnRH agonists work by causing the LH surge (release of LH from the pituitary). Recall that it is the LH surge that triggers ovulation.

Fresh transfer protocols

Fresh transfer protocols are used in order to both retrieve eggs and attempt pregnancy within the same cycle. A fresh embryo is selected and transferred into the uterus at either Day 3 or Day 5 post-retrieval. Any remaining embryos are cryopreserved for upcoming FET cycles.lviii

One concern of fresh embryo transfer is an increased risk of OHSS, which is the leading cause of morbidity in IVF treatment and, in rare cases, can even lead to death (an estimated 3 deaths per 100,000 cycles). The use of hCG to trigger ovulation in COS can result in increased permeability (leakiness) of the blood vessels. This side effect causes the ovaries to swell and leak fluid into the body, causing pain, shortness of breath, swelling, bloating, increased risk of blood clots, and nausea among other symptoms. Frozen embryo transfer protocols prevent OHSS by eliminating ovarian hyperstimulation.lix

Frozen transfer protocols

In a patient undergoing embryo transfer with frozen embryos, hormone therapy is typically required to prepare the lining of the uterus to receive the embryo for implantation. This process starts with taking estrogen such as Estrace® on days one to three of the cycle.lx Progesterone is then administered to make the uterus receptive to implantation of the embryo. It is commonly administered by intramuscular injection of progesterone in oil (PIO).lxi However, it can also be administered using vaginal suppositories such as Endometrin® or Prometrium®.lxii In natural FET cycles, often no medications are needed; however, many patients still use vaginal progesterone for luteal-phase support after spontaneous ovulation is confirmed.

Other drugs

Other drugs may also be used for embryo transfer to support a specific aspect of the process. Some of the most common drugs used during this point of IVF are below.

Prednisone

Prednisone is a steroid medication that is involved in modulating the activity of the immune system. Multiple studies have shown that prednisone can suppress the activity of certain immune cells within the uterus and promote embryo implantation.lxiii However, the use of prednisone in embryo transfer is still being debated and should be used on a case-by-case basis. A study by Robertson et al. (2016) argues that it should only be used if identified immune dysfunction is present.lxiv A 2023 randomized clinical trial found prednisone did not significantly improve live birth rates in females who had previously experienced two or more unsuccessful embryo transfers in comparison to the placebo-only group.lxv

Intralipids

Intralipid infusions are an emulsion of fats given intravenously. They have been hypothesized to suppress natural killer (NK) immune cell activity for patients with recurrent implantation failure (RIF) in IVF. The effectiveness of intralipids is still controversial. A 2020 review study concluded that intralipids may improve outcomes in females with previous implantation failures, but the results did not show any significant differences in live birth rates with or without intralipids.lxvi Meanwhile, a 2021 meta-analysis examining data from five randomized control trials including 840 patients found intralipid infusion improved clinical pregnancy rate, ongoing pregnancy rate, and live birth rate, but did not improve miscarriage rate.lxvii

Metformin

Metformin (Glumetza®, Fortamet®, Glucophage®) is an oral medication that is often used in patients with polycystic ovary syndrome (PCOS) to improve the body’s sensitivity to insulin and decrease excess androgen production (e.g., testosterone). One study observed that metformin increased pregnancy rates for PCOS patients with a BMI of 26 or greater.lxviii However, a Cochrane review by Tso et al. (2020) involving a total of 1,132 females with PCOS found no conclusive evidence to support the use of metformin to improve live birth rates.lxix

Metformin has also been investigated for use in cycles where premature luteinization occurs. Premature luteinization is when progesterone levels become elevated earlier in the IVF cycle than they should. (Progesterone levels should be very low prior to ovulation,lxx discussed below.) A 2021 randomized double-blind controlled trial investigated the effect of metformin (shown to decrease progesterone levels) on cycle outcome.lxxi The aim of adding metformin was to prevent premature luteinization during ICSI cycles followed by a fresh transfer. Researchers found that metformin significantly decreased the occurrence of premature luteinization (10 percent vs. 23.6 percent in the control group). Further, the metformin group produced a higher number of good-quality embryos and had a higher rate of ongoing pregnancy in comparison to patients who did not receive metformin treatment.

Heparin and derivatives

Enoxaparin (Lovenox®, Clexane®) is a type of blood thinner medication that acts as an anticoagulant, meaning that it prevents blood clots from forming. Heparins are sometimes used in patients with RIF or known thrombophilia (increased chance of blood clots), with the intent of improving implantation rate.lxxii The utility of heparin in embryo transfer remains controversial. A small 2018 study of 83 females with known thrombophilia found that live birth rates were increased with enoxaparin 40 mg/day treatment (24 percent) compared to controls (no enoxaparin, 3 percent).lxxiii

However, when analyzing females with no known clotting issues, a 2018 meta-analysis found no difference in outcomes when heparins were used.lxxiv,lxxv

What happens on embryo transfer day?

Patients are usually instructed to arrive approximately 45 minutes before the embryo transfer. During the procedure, a speculum is inserted into the vagina to visualize the cervix. The cervix is cleaned. Then, a catheter is inserted through the opening into the uterus so that the embryo can be loaded and transferred through the catheter. The process is typically not painful, but some patients experience mild discomfort and cramping. The entire process is typically completed without sedation.lxxvi

The embryo transfer is most often completed using ultrasound for direct visualization.lxxvii Patients are instructed to drink water prior to the appointment to fill their bladder, which improves the ultrasound image. The ultrasound probe is usually placed over the abdomen and allows the physician to see the placement of the catheter in the uterus. Then, the doctor can directly observe the location of the transferred embryo(s) and confirm that it is placed in the correct location to maximize chances of implantation and pregnancy.lxxviii At many clinics, air bubbles are inserted into the catheter before and after the embryo. These bubbles help visualize the entry of the embryo into the uterus on the ultrasound.lxxix,lxxx

Embryo transfer ultrasound
An ultrasound probe helps visualize the embryo transfer via catheter

Once the ultrasound is complete, the embryologist will check to ensure that the embryo did in fact get transferred to the uterus and did not get “stuck” in the catheter. If one or more embryos were retained in the catheter, the transfer process is repeated immediately. Studies have shown that there is no impact on success rates when this issue occurs in cleavage-stage embryo or blastocyst transfers.lxxxi The insertion of the catheter is typically done very slowly and gently in order to prevent uterine cramping, which can potentially lead to expulsion of the embryo from the uterus.lxxxii

Fertility clinics generally advise that the actual transfer procedure takes five to 15 minutes. Many clinics will allow patients to watch the transfer on a large monitor. They may also provide photos of the embryos to be transferred, and/or allow individuals to take pictures of the monitor.

What should you do after embryo transfer during the two-week wait (TWW)?

Medical providers will give direct instructions on what to do in the days following the protocol to support successful embryo transfer and implantation.

Some older research suggested that bed rest was necessary following embryo transfer, but more recent evidence does not support this recommendation. A study by Frankel et al. (2016) found no significant difference in implantation rates between the bed-rest group (65 percent) versus the group that moved around immediately after transfer (66 percent).lxxxiii

Some clinics recommend abstaining from intercourse after embryo transfer due to the potential for infection and the possibility of an additional conception. However, there is also evidence suggesting that intercourse around the time of transfer, specifically exposure to semen, may improve clinical pregnancy rates. An argument for abstaining is that sexual intercourse during TWW poses the risk of an additional pregnancy. A heterotopic pregnancy occurs when there is one pregnancy in the uterus and one outside of the uterus (e.g., fallopian tube), which poses serious complications.lxxxiv,lxxxv In addition, a 2014 study observed that patients who had sexual intercourse in the days following embryo transfer had higher odds of miscarrying.lxxxvi

Conversely, some studies indicate that seminal plasma interacts with the endometrium to promote immune regulation and tolerance, therefore facilitating implantation.lxxxvii,lxxxviii Data from various studies suggests that exposure to seminal fluid around the time of embryo transfer can improve clinical pregnancy rates compared to females not exposed to seminal fluid.lxxxix,xc,xci Overall, there is a lack of consensus as to whether sexual intercourse, and exposure to semen, may increase or decrease chances of IVF success. There is currently a randomized controlled trial recruiting patients in an attempt to answer this question.xcii

Most clinics will also suggest avoiding things such as alcohol, certain undercooked foods, heavy lifting, and some types of exercise.

What happens on beta test day?

The hormone hCG is tested in a home urinary pregnancy test. It is one of the earliest markers of embryonic implantation and may be present in a female’s urine and/or blood by six to eight days after implantation occurs. However, blood levels of beta-hCG are typically tested nine to 14 days after embryo transfer.xciii In fresh embryo transfer, data from several studies suggested that a beta-hCG level of 111 to 213 IU/L at 10 to 12 days after fresh blastocyst transfer was a good indicator to predict an ongoing pregnancy.xciv In frozen embryo transfer, the beta-hCG threshold was 137 to 399 IU/L in predicting successful pregnancy at 10 to 12 days.

Progesterone is often tested on the day the beta test is completed, as it is important for maintaining a pregnancy once it occurs. Progesterone modulates a female’s immune system, preventing the uterus from contracting, and allowing for good circulation between the uterus and the placenta. A study by Kim et al. (2020) suggests that a progesterone level of at least 25.3 ng/mL 14 days after embryo transfer is associated with a higher rate of ongoing pregnancy.xcv Progesterone levels on the day of beta-hCG are higher than on transfer day (discussed above). If progesterone levels are low, physicians may increase the dosage of progesterone supplementation.

Pregnancy and next steps

After embryos are transferred, care providers will continue to monitor hormone levels and wait for the fetal heartbeat to be detected to confirm pregnancy. In a normally progressing pregnancy, the beta-hCG is expected to approximately double every 48 hours.xcvi

Biochemical pregnancies and ectopic pregnancies are also possible in the weeks following implantation, punctuating the importance of continuous monitoring. A chemical pregnancy is a pregnancy loss that occurs after heightened hCG levels have been detected, but before an embryo can be detected by ultrasound.xcvii

The fetal heart rate is usually detectable on ultrasound by a gestational age of approximately 6.5 weeks.xcviii In most cases, discharge from the fertility clinic to an obstetrician occurs at about 10 weeks’ gestation.xcix

No pregnancy and next steps

After a negative beta-hCG test, the physician will likely suggest that the patient stops transfer medications, though all should medications be continued until directed by a physician. The patient will usually begin menstrual bleeding within a few days of stopping medication, although the exact number of days is variable.

If a female has frozen embryos, her next steps after a negative beta-hCG test will likely be to try another FET with or without additional testing. Some females do an FET in the next cycle, while others wait. If there are no frozen embryos remaining after an unsuccessful transfer cycle, another IVF cycle can be tried. Although the process may be discouraging, a study by Smith et al. (2025) of 156,947 females showed that approximately 63 percent of females under 40 achieved a live birth by the third IVF cycle.c In this study, an IVF cycle is defined as one egg retrieval and transfer of all embryos made from the eggs retrieved.

A female can try a second egg retrieval cycle directly following a failed cycle, although some evidence indicates it may be better to wait. One study by Reichman et al. (2012) compared 192 females who started a second cycle fewer than 55 days from their previous egg retrieval to 557 females who started a second cycle between 56 to 140 days following their prior egg retrieval.ci They found that the rate of implantation was slightly lower in the former group (9 percent) compared to the latter (13 percent).

Conclusion  

While every IVF cycle may not result in pregnancy, the technology continues to grow more advanced and rates of successful pregnancies with IVF have grown substantially. Becoming familiar with what to expect helps ensure the embryo transfer process has the best chance of a positive outcome. While the process can be physically and mentally challenging, advanced preparation, education, and understanding will help.

November 18, 2024

Medically Reviewed by

Dr. Kelly McCarter, MD

September 29, 2022

Medically Reviewed by

Dr. Brent Monseur MD, ScM

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ii Acharya, K. S., et al. (2018). Freezing of all embryos in in vitro fertilization is beneficial in high responders, but not intermediate and low responders: An analysis of 82,935 cycles from the society for assisted reproductive technology registry. Fertility and Sterility, 110(5), 880-887. https://doi.org/10.1016/j.fertnstert.2018.05.024

iii Letterie, G., et al. (2005). The relationship of clinical response, oocyte number, and success in oocyte donor cycles. Journal of Assisted Reproduction and Genetics, 22(3), 115-117. https://doi.org/10.1007/s10815-005-4875-9

iv Elder, K., & Dale, B. (2010). In-vitro fertilization. Cambridge University Press. https://doi.org/10.1017/9781108611633.007

v Wong, K. M., et al. (2021). Transfer of fresh or frozen embryos: A randomised controlled trial. Human Reproduction, 36(4), 998-1006. https://doi.org/10.1093/humrep/deaa305

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vii Coates, A., et al. (2017). Optimal euploid embryo transfer strategy, fresh versus frozen, after preimplantation genetic screening with next generation sequencing: A randomized controlled trial. Fertility and Sterility, 107(3), 723-730.e3. https://doi.org/10.1016/j.fertnstert.2016.12.022

viii Montagut, M., et al. (2016). Frozen–thawed embryo transfers in natural cycles with spontaneous or induced ovulation: The search for the best protocol continues. Human Reproduction, 31(12), 2803-2810. https://doi.org/10.1093/humrep/dew263

ix Buzaglo, K., et al. (2012). Leading follicle size in modified natural cycle IVF- predictor of successful outcome? Fertility and Sterility, 98(3), S267. https://doi.org/10.1016/j.fertnstert.2012.07.972

x Montagut, M., et al. (2016). Frozen–thawed embryo transfers in natural cycles with spontaneous or induced ovulation: The search for the best protocol continues. Human Reproduction, 31(12), 2803-2810. https://doi.org/10.1093/humrep/dew263

xi Li, D., et al. (2021). Frozen embryo transfer in mildly stimulated cycle with Letrozole compared to natural cycle in Ovulatory women: A large retrospective study. Frontiers in Endocrinology, 12. https://doi.org/10.3389/fendo.2021.677689

xii Mumusoglu, S., et al. (2021). Preparation of the endometrium for frozen embryo transfer: A systematic review. Frontiers in Endocrinology, 12. https://doi.org/10.3389/fendo.2021.688237

xiii Mumusoglu, S., et al. (2021). Preparation of the endometrium for frozen embryo transfer: A systematic review. Frontiers in Endocrinology, 12. https://doi.org/10.3389/fendo.2021.688237

xiv Devine, K., et al. (2021). Intramuscular progesterone optimizes live birth from programmed frozen embryo transfer: a randomized clinical trial. Fertility and Sterility, 116(3), pp.633–643. https://doi.org/10.1016/j.fertnstert.2021.04.013

xv Flores, V., et al. (2017). Trilaminar endometrial pattern correlates with higher clinical pregnancy rates in frozen embryo transfer cycles. Fertility and Sterility, 108(3), e358. https://doi.org/10.1016/j.fertnstert.2017.07.1049

xvi Haas, J., et al. (2019). Endometrial compaction (decreased thickness) in response to progesterone results in optimal pregnancy outcome in frozen-thawed embryo transfers. Fertility and Sterility, 112(3), 503-509.e1. https://doi.org/10.1016/j.fertnstert.2019.05.001

xvii Bosch, E., Valencia, I., Escudero, E., et al. (2003). Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome. Fertility and Sterility, 80(6), pp.1444–1449. https://doi.org/10.1016/j.fertnstert.2003.07.002

xviii Casper, R. F., & Yanushpolsky, E. H. (2016). Optimal endometrial preparation for frozen embryo transfer cycles: Window of implantation and progesterone support. Fertility and Sterility, 105(4), 867-872. https://doi.org/10.1016/j.fertnstert.2016.01.006

xix Kaponis, A., et al. (2018). The curious case of premature luteinization. Journal of Assisted Reproduction and Genetics, 35(10), 1723-1740. https://doi.org/10.1007/s10815-018-1264-8

xx Venetis, C., et al. (2013). Progesterone elevation and probability of pregnancy after IVF: A systematic review and meta-analysis of over 60 000 cycles. Human Reproduction Update, 19(5), 433-457. https://doi.org/10.1093/humupd/dmt014

xxi Venetis, C., et al. (2013). Progesterone elevation and probability of pregnancy after IVF: A systematic review and meta-analysis of over 60 000 cycles. Human Reproduction Update, 19(5), 433-457. https://doi.org/10.1093/humupd/dmt014

xxii Kofinas, J. D., et al. (2015). Serum progesterone levels greater than 20 Ng/dl on day of embryo transfer are associated with lower live birth and higher pregnancy loss rates. Journal of Assisted Reproduction and Genetics, 32(9), 1395-1399. https://doi.org/10.1007/s10815-015-0546-7

xxiii Brady, P. C., et al. (2014). Serum progesterone concentration on day of embryo transfer in donor oocyte cycles. Journal of Assisted Reproduction and Genetics, 31(5), 569-575. https://doi.org/10.1007/s10815-014-0199-y

xxiv Kofinas, J. D., et al. (2015). Serum progesterone levels greater than 20 Ng/dl on day of embryo transfer are associated with lower live birth and higher pregnancy loss rates. Journal of Assisted Reproduction and Genetics, 32(9), 1395-1399. https://doi.org/10.1007/s10815-015-0546-7

xxv Brady, P. C., et al. (2014). Serum progesterone concentration on day of embryo transfer in donor oocyte cycles. Journal of Assisted Reproduction and Genetics, 31(5), 569-575. https://doi.org/10.1007/s10815-014-0199-y

xxvi Diluigi, A., et al. (2005). Serum Estradiol level on day of embryo transfer is associated with implantation and pregnancy rates. Fertility and Sterility, 84, S265. https://doi.org/10.1016/j.fertnstert.2005.07.688

xxvii Alur-Gupta, S., et al. (2020). Measuring serum estradiol and progesterone one day prior to frozen embryo transfer improves live birth rates. Fertility Research and Practice, 6(1). https://doi.org/10.1186/s40738-020-00075-2

xxviii Zhang, Y., et al. (2020). The impact of TSH levels on clinical outcomes 14 days after frozen-thawed embryo transfer. BMC Pregnancy and Childbirth, 20(1). https://doi.org/10.1186/s12884-020-03383-z

xxix Reinblatt, S., et al. (2013). Thyroid stimulating hormone levels rise after assisted reproductive technology. Journal of Assisted Reproduction and Genetics, 30(10), 1347-1352. https://doi.org/10.1007/s10815-013-0081-3

xxx Gao, G., et al. (2020). Endometrial thickness and IVF cycle outcomes: A meta-analysis. Obstetrical & Gynecological Survey, 75(5), 296-297. https://doi.org/10.1097/01.ogx.0000666660.15958.43

xxxi Flores, V., et al. (2017). Trilaminar endometrial pattern correlates with higher clinical pregnancy rates in frozen embryo transfer cycles. Fertility and Sterility, 108(3), e358. https://doi.org/10.1016/j.fertnstert.2017.07.1049

xxxii Yan, J., et al. (2012). Effect of maternal age on the outcomes of in vitro fertilization and embryo transfer (IVF-ET). Science China Life Sciences, 55(8), 694-698. https://doi.org/10.1007/s11427-012-4357-0

xxxiii Greco, E., et al. (2020). Preimplantation genetic testing: Where we are today. International Journal of Molecular Sciences, 21(12), 4381. https://doi.org/10.3390/ijms21124381

xxxiv Fox, C., et al. (2016). Local and systemic factors and implantation: What is the evidence? Fertility and Sterility, 105(4), 873-884. https://doi.org/10.1016/j.fertnstert.2016.02.018

xxxv Boynukalin, F. K., et al. (2020). Impact of elective frozen vs. fresh embryo transfer strategies on cumulative live birth: Do deleterious effects still exist in normal & hyper responders? PLOS ONE, 15(6), e0234481. https://doi.org/10.1371/journal.pone.0234481

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xxxvii Cheung, W. J. K., et al. (2021). Young eggs in an old basket – is there a maternal age limit for embryo transfer? Fertility and Sterility, 116(3), e250-e251. https://doi.org/10.1016/j.fertnstert.2021.07.672

xxxviii Greco, E., et al. (2020). Preimplantation genetic testing: Where we are today. International Journal of Molecular Sciences, 21(12), 4381. https://doi.org/10.3390/ijms21124381

xxxix Greco, E., et al. (2020). Preimplantation genetic testing: Where we are today. International Journal of Molecular Sciences, 21(12), 4381. https://doi.org/10.3390/ijms21124381

xl Rubio, C., et al. (2017). In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: A randomized, controlled study. Fertility and Sterility, 107(5), 1122-1129. https://doi.org/10.1016/j.fertnstert.2017.03.011

xli Anderson, R., et al. (2020). Clinical benefits of preimplantation genetic testing for aneuploidy (PGT-A) for all in vitro fertilization treatment cycles. European Journal of Medical Genetics, 63(2), 103731. https://doi.org/10.1016/j.ejmg.2019.103731

xlii Sanders, K. D., et al. (2021). Analysis of IVF live birth outcomes with and without preimplantation genetic testing for aneuploidy (PGT-A): UK human fertilisation and embryology authority data collection 2016–2018. Journal of Assisted Reproduction and Genetics, 38(12), 3277-3285. https://doi.org/10.1007/s10815-021-02349-0

xliii Sato, T., et al. (2019). Preimplantation genetic testing for aneuploidy: A comparison of live birth rates in patients with recurrent pregnancy loss due to embryonic aneuploidy or recurrent implantation failure. Human Reproduction, 34(12), 2340-2348. https://doi.org/10.1093/humrep/dez229

xliv Yan J, et al. (2021). “Live Birth with or without Preimplantation Genetic Testing for Aneuploidy.” N Engl J Med. 385: 2047-1058.  

xlv Munné, S., et al. (2019). Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial. Fertility and sterility, 112(6), 1071–1079.e7. https://doi.org/10.1016/j.fertnstert.2019.07.1346

xlvi Patrizio, P., et al. (2019). Worldwide live births following the transfer of chromosomally “Abnormal” embryos after PGT/A: Results of a worldwide web-based survey. Journal of Assisted Reproduction and Genetics, 36(8), 1599-1607. https://doi.org/10.1007/s10815-019-01510-0

xlvii Gordon, C. E., et al. (2022). Embryo attrition in planned PGT-A: predicting the number of available blastocysts for transfer. Journal of assisted reproduction and genetics, 39(1), 173–181. https://doi.org/10.1007/s10815-021-02365-0

xlviii Wong, K. M., et al. (2017). Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database of Systematic Reviews, 3(3), CD011184. https://doi.org/10.1002/14651858.cd011184.pub2

xlix Boynukalin, F. K., et al. (2020). Impact of elective frozen vs. fresh embryo transfer strategies on cumulative live birth: Do deleterious effects still exist in normal & hyper responders? PLOS ONE, 15(6), e0234481. https://doi.org/10.1371/journal.pone.0234481

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lii Herman, H.G., et al. (2022). Obstetric and Perinatal Outcomes of Pregnancies Resulting from Fresh Versus Frozen Embryo Transfer—a Sibling Cohort. Reproductive Sciences, 29(5), pp.1644–1650. https://doi.org/10.1007/s43032-021-00570-x

liii Glujovsky, D., et al. (2016). Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.cd002118.pub5

liv Hatırnaz, Ş., & Kanat Pektaş, M. (2017). Day 3 embryo transfer versus day 5 blastocyst transfers: A prospective randomized controlled trial. Journal of Turkish Society of Obstetric and Gynecology, 14(2), 82-88. https://doi.org/10.4274/tjod.99076

lv Mumusoglu, S., et al. (2021). Preparation of the endometrium for frozen embryo transfer: A systematic review. Frontiers in Endocrinology, 12. https://doi.org/10.3389/fendo.2021.688237

lvi Mumusoglu, S., et al. (2021). Preparation of the endometrium for frozen embryo transfer: A systematic review. Frontiers in Endocrinology, 12. https://doi.org/10.3389/fendo.2021.688237

lvii Alyasin, A., et al. (2016). GnRH agonist trigger versus hCG trigger in GnRH antagonist in IVF/ICSI cycles: A review article. International Journal of Reproductive BioMedicine, 14(9), 557-566. https://doi.org/10.29252/ijrm.14.9.557

lviii Wong, K. M., et al. (2017). Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database of Systematic Reviews, 3(3), CD011184. https://doi.org/10.1002/14651858.cd011184.pub2

lix Evans, J., et al. (2014). Fresh versus frozen embryo transfer: Backing clinical decisions with scientific and clinical evidence. Human Reproduction Update, 20(6), 808-821. https://doi.org/10.1093/humupd/dmu027

lx Madero, S., et al. (2016). Endometrial preparation: Effect of estrogen dose and administration route on reproductive outcomes in oocyte donation cycles with fresh embryo transfer. Human Reproduction, 31(8), 1755-1764. https://doi.org/10.1093/humrep/dew099

lxi Devine K, Richter KS, Jahandideh S, Widra EA, McKeeby JL. Intramuscular progesterone optimizes live birth from programmed frozen embryo transfer: a randomized clinical trial. Fertil Steril. 2021 Sep;116(3):633-643. doi: 10.1016/j.fertnstert.2021.04.013. Epub 2021 May 13. PMID: 33992421.

lxii Mumusoglu, S., et al. (2021). Preparation of the endometrium for frozen embryo transfer: A systematic review. Frontiers in Endocrinology, 12. https://doi.org/10.3389/fendo.2021.688237

lxiii Lu, Y., et al. (2020). Prednisone for patients with recurrent implantation failure: Study protocol for a double-blind, multicenter, randomized, placebo-controlled trial. Trials, 21(1). https://doi.org/10.1186/s13063-020-04630-6

lxiv Robertson, S. A., et al. (2016). Corticosteroid therapy in assisted reproduction – immune suppression is a faulty premise. Human Reproduction, 31(10), 2164-2173. https://doi.org/10.1093/humrep/dew186

lxv Sun, Y., et al. (2023). Prednisone vs Placebo and Live Birth in Patients With Recurrent Implantation Failure Undergoing In Vitro Fertilization. JAMA, 329(17), pp.1460–1460. https://doi.org/10.1001/jama.2023.5302

lxvi Zhou, P., et al. (2020). The effect of intralipid on pregnancy outcomes in women with previous implantation failure in in vitro fertilization/intracytoplasmic sperm injection cycles: A systematic review and meta-analysis. European Journal of Obstetrics & Gynecology and Reproductive Biology, 252, 187-192. https://doi.org/10.1016/j.ejogrb.2020.06.057

lxvii Han, E.J., et al. (2021). Efficacy of intralipid administration to improve in vitro fertilization outcomes: A systematic review and meta-analysis. Daehan saengsik uihak hoeji/Clinical and experimental reproductive medicine, 48(3), pp.203–210. https://doi.org/10.5653/cerm.2020.04266

lxviii Wu, Y., et al. (2020). Association of metformin with pregnancy outcomes in women with polycystic ovarian syndrome undergoing in vitro fertilization. JAMA Network Open, 3(8), e2011995. https://doi.org/10.1001/jamanetworkopen.2020.11995

lxix Tso, L. O., et al. (2020). Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome. Cochrane Database of Systematic Reviews, 2020(12). https://doi.org/10.1002/14651858.cd006105.pub4

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lxxi Hussein, R.S., et al. (2021). Effect of Metformin on Premature Luteinization and Pregnancy Outcomes in Intracytoplasmic Sperm Injection-Fresh Embryo Transfer Cycles: A Randomized Double-Blind Controlled Trial. PubMed, 15(2), pp.108–114. https://doi.org/10.22074/ijfs.2020.134643

lxxii Hamdi, K., et al. (2015). The role of Heparin in embryo implantation in women with recurrent implantation failure in the cycles of assisted reproductive techniques (without history of Thrombophilia). Journal of Family and Reproductive Health, 9(2), 59-64.

lxxiii Qublan, H., et al. (2008). Low-molecular-weight heparin in the treatment of recurrent IVF–ET failure and thrombophilia: A prospective randomized placebo-controlled trial. Human Fertility, 11(4), 246-253. https://doi.org/10.1080/14647270801995431

lxxiv Yang, X., et al. (2018). Efficacy of low-molecular-weight heparin on the outcomes of in vitro fertilization/intracytoplasmic sperm injection pregnancy in non-thrombophilic women: A meta-analysis. Acta Obstetricia et Gynecologica Scandinavica, 97(9), 1061-1072. https://doi.org/10.1111/aogs.13359

lxxv Hamdi, K., et al. (2015). The role of Heparin in embryo implantation in women with recurrent implantation failure in the cycles of assisted reproductive techniques (without history of Thrombophilia). Journal of Family and Reproductive Health, 9(2), 59-64.  

lxxvi Schoolcraft, W. B. (2016). Importance of embryo transfer technique in maximizing assisted reproductive outcomes. Fertility and Sterility, 105(4), 855-860. https://doi.org/10.1016/j.fertnstert.2016.02.022

lxxvii Nastri, C. O., & Martins, W. P. (2016). Ultrasound guidance for embryo transfer: Where do we stand? Ultrasound in Obstetrics & Gynecology, 48(3), 279-281. https://doi.org/10.1002/uog.16005

lxxviii Revelli, A., et al. (2016). Large randomized trial comparing transabdominal ultrasound-guided embryo transfer with a technique based on uterine length measurement before embryo transfer. Ultrasound in Obstetrics & Gynecology, 48(3), 289-295. https://doi.org/10.1002/uog.15899

lxxix Zinger, M., et al. (2004). Movement of intrauterine air bubble during embryo transfer (ET) catheter withdrawal is not a prognostic indicator. Fertility and Sterility, 82, S63. https://doi.org/10.1016/j.fertnstert.2004.07.161

lxxx Nastri, C. O., & Martins, W. P. (2016). Ultrasound guidance for embryo transfer: Where do we stand? Ultrasound in Obstetrics & Gynecology, 48(3), 279-281. https://doi.org/10.1002/uog.16005

lxxxi Yi, H. J., et al. (2016). Reproductive outcomes of retransferring retained embryos in blastocyst transfer cycles. Clinical and Experimental Reproductive Medicine, 43(2), 133. https://doi.org/10.5653/cerm.2016.43.2.133

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lxxxiii Frankel, A., et al. (2016). Immediate ambulation after embryo transfer has no effect on ongoing pregnancy rates in fresh or frozen IVF cycles with or without comprehensive chromosomal screening. Fertility and Sterility, 106(3), e206. https://doi.org/10.1016/j.fertnstert.2016.07.595

lxxxiv Aoki, Y., et al. (2017). Should sexual intercourse be avoided during the embryo transfer cycle? Life-threatening ruptured heterotopic pregnancy after single thawed embryo transfer: case report and review of the literature. Clinical and Experimental Obstetrics and Gynecology, 44(3), 489-491. https://doi.org/10.12891/ceog3647.2017

lxxxv Sato, T., et al. (2019). Preimplantation genetic testing for aneuploidy: A comparison of live birth rates in patients with recurrent pregnancy loss due to embryonic aneuploidy or recurrent implantation failure. Human Reproduction, 34(12), 2340-2348. https://doi.org/10.1093/humrep/dez229

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lxxxvii Sharkey, D. J., et al. (2012). Seminal fluid induces leukocyte recruitment and Cytokine and Chemokine mRNA expression in the human cervix after coitus. The Journal of Immunology, 188(5), 2445-2454. https://doi.org/10.4049/jimmunol.1102736

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xcviii Arleo, K. E., & Troiano, R. N. (2011). Outcome of early first-trimester pregnancies (<6.1 weeks) with slow embryonic heart rate. Obstetrical & Gynecological Survey, 66(10), 607-608. https://doi.org/10.1097/ogx.0b013e318233118d

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