Antagonist regimen, PPOS regimen, and luteal phase ovarian stimulation are often discussed together. The first two mainly describe how to suppress the early luteinizing hormone (LH) peak, and luteal phase ovarian stimulation describes which stage of the menstrual cycle starts stimulating follicles. Only by understanding these two classification perspectives can we see clearly the actual trade-offs between the protocols.
Protocol names and mechanisms
First, distinguish whether the name refers to the starting time or the LH-surge suppression medication.
stimulation timing and LH-surge suppression medication
PPOS is the abbreviation of progestin-primed ovarian stimulation, usually translated as progestin pretreatment to stimulate ovulation or ovulation in a high progesterone state. Their common feature is the use of exogenous progestins during ovarian stimulation to prevent premature LH surges. Conventional PPOS uses medication from the beginning of stimulation, and there are also flexible starting variants. All PPOS cannot be understood as the same fixed schedule.
GnRH antagonists inhibit LH release by acting on GnRH receptors in the pituitary gland. A luteal-phase start means beginning ovarian stimulation after ovulation: endogenous progesterone can participate in suppressing the LH peak. As the luteal function changes, the doctor may use progestins, antagonists or other specific arrangements. The name "luteal phase" cannot be used to judge the entire medication. [1][14]
How LH-surge suppression affects transfer options
The goal of ovarian stimulation is to develop a group of follicles that respond to exogenous gonadotropins. Trigger drugs are given at the appropriate time to trigger the final maturation of oocytes, and then egg retrieval is arranged. Follicular growth accompanied by an increase in estradiol may induce a premature LH surge; if ovulation occurs before planned egg retrieval, the number of available oocytes will be reduced and some cycles may be cancelled.
The losses caused by early ovulation require particular attention when only a few follicles are expected to develop. A single rise in LH, sustained LH surge, premature ovulation, and cycle cancellation are different endpoints and are not interchangeable. Which endpoint is reported in the study directly determines how far the conclusion can be extended.
GnRH antagonist
GnRH antagonists competitively bind to the GnRH receptor in the pituitary gland and have a rapid onset of action. The common method of administration is subcutaneous injection. Clinically, there are fixed plans based on the number of days of stimulation, and flexible plans based on the start of follicular development. The timing and duration of medication are determined by your doctor.
The ESHRE 2025 updated guidelines recommend that the general IVF/ICSI population give priority to the use of antagonist regimens on the grounds that they are similar in efficacy to agonist regimens but have higher safety. Strong recommendation ⊕⊕⊕○; the guidelines also give a conditional recommendation for fixed antagonist regimens over flexible regimens. Antagonist cycles can be triggered by triggers such as hCG or GnRH agonists based on risk and transfer plan. The trigger cannot be determined by the name of the regimen alone. [1]
Progestin-based LH-surge suppression
Progesterone regulates GnRH and LH secretion through feedback to the hypothalamus-pituitary gland, preventing the formation of premature LH peaks during ovarian stimulation. Commonly used oral medications include medroxyprogesterone acetate and dydrogesterone. The medicine, starting date and taking method should be carried out according to the prescription. If you miss a dose, you should contact the clinic in time.
The major process limitation in PPOS arises from the endometrium. Giving progesterone in advance during the ovarian stimulation stage can cause the timing of endometrium and embryo development after egg retrieval to be inconsistent. Therefore, fresh embryo transfer is usually not arranged in this cycle: the available embryos obtained are frozen and transferred in subsequent cycles; if the purpose is to freeze eggs, freeze oocytes. The restrictions mentioned here apply to the fresh embryo transfer of the person undergoing ovarian stimulation. [1]
ESHRE's recommendation on PPOS is based on the premise that freeze-all has been planned. It is a conditional recommendation and the certainty of the evidence is very low⊕○○○. A freeze-all strategy is not a step required for all patients, nor is it a uniform approach to improving success rates. [1][15]
Timing of initiation in the menstrual cycle
The physiological basis for non-conventional starts, and the conditions set for them by guidelines.
Follicular growth wave and unconventional initiation
A 2003 study that followed continuous ultrasound observations of healthy women throughout their menstrual cycles documented that two to three follicular growth waves could be present during a cycle. It can be seen that antral follicles do not only appear at the beginning of menstruation, but there can also be groups of follicles that respond to stimulation during the luteal phase. [10]
This provides a physiological basis for luteal-phase start, random initiation and dual stimulation. It shows that you can try to change the starting point of ovarian stimulation, but it cannot guarantee that the same number or quality of oocytes will be obtained at every time point, nor can it be deduced that multiple stimulations will definitely increase the live birth rate.
One of the immediate uses of random start is to reduce the time to wait for the next menstrual period in time-constrained situations. It is still necessary to evaluate the ovarian and hormonal status before starting the cycle, and to rule out or deal with possible risks of natural conception. [1][14]
Common start strategies and guideline conditions
Start strategies and their scope in the ESHRE 2025 guideline update
| Strategy | Description | Scope of application of the guidelines |
|---|---|---|
| Regular follicular phase initiation | Stimulation usually begins on day 2 to 3 of menstruation | Routine arrangement; whether fresh embryo transfer can be performed depends on specific medications and clinical conditions |
| Random start | It is not limited to starting from early menstruation, it can be started at different cycle stages | Can be used when fresh embryo transfer is not planned; risks associated with simultaneous natural conception need to be discussed Good Practice Statement [1] |
| Start of luteal phase | Stimulation begins during the luteal phase after ovulation | It can be used when fresh embryo transfer is not planned and there is no possibility of natural conception. Conditional recommendation ⊕○○○[1] |
| Initiate late luteal phase and plan fresh embryo transfer | Start gonadotropins in the late luteal phase, and then arrange for fresh embryo transfer | May not be recommended for low responders Conditionally recommended ⊕○○○[1] |
| double stimulation | Two stimulations and two egg retrievals in the same ovarian cycle | Can be used to accumulate eggs or embryos when fresh embryo transfer is not planned. Strong recommendation ⊕⊕○○; Emergency fertility preservation is a good practice statement [1] |
Strength of recommendation and certainty of evidence are two indicators. "Strong recommendation" does not mean that there is high-certainty evidence of efficacy.
These conditions are used to define guideline-supported clinical arrangements. "It can be used when fresh embryo transfer is not planned" cannot be rewritten to mean that all unconventional starts are physiologically absolutely impossible for fresh embryo transfer. A more practical question for the reader is why our center chose this launch date and what impact it will have on subsequent transfers.
Benefits and uncertainties in controlled studies
Before looking at the results, confirm the population, control protocol, and endpoints.
Comparison of PPOS and Antagonists
Different studies may compare LH-surge suppression drugs, or the entire process including fresh embryo or frozen embryo transfer. The conclusions drawn from these two types of comparisons are not interchangeable.
Systematic review of randomized trials
A review published in "Ultrasound in Obstetrics & Gynecology" in 2026 included 20 randomized controlled trials with a total of 4430 people. Seventeen of these compared PPOS with antagonists, and three compared agonists or agonist plus antagonist regimens. Compared with antagonists, PPOS first embryo transfer cycles had better live birth outcomes, with a relative risk of live birth of 1.13 (95% CI 1.02–1.25) and an average of 0.88 more oocytes retrieved (95% CI 0.27–1.50). The certainty of evidence for these two outcomes was moderate and low, respectively. [2]
The included trials were all randomized, but none were rated as having low overall risk of bias: 13 were of some concern and 7 were high risk. The review also found no significant difference in the oocyte retrieval cancellation rate or premature LH peak incidence between the two regimens, and the results cannot be generalized to mean that PPOS is superior in all endpoints. [2]
A randomized trial in a population with normal ovarian reserve
An open-label randomized controlled trial in 2024 included 348 first-time IVF women with normal ovarian reserve. 174 received PPOS plus freeze-all, and 174 received antagonist with priority for fresh embryo transfer. The cumulative live birth rate was 55.75% vs. 52.87%, the difference was not statistically significant (P=0.591). [11]
Six people in the antagonist group, accounting for 3.45%, had premature LH elevation; this was not observed in the PPOS group, but there was no premature ovulation in either group. This result cannot be directly converted into a difference in the risk of premature ovulation or cycle cancellation. The trial compared two complete processes, and the cumulative live birth results cannot be attributed entirely to peak suppressing drugs. [11]
Retrospective cohort of PGT cycles
A retrospective study that included 865 preimplantation genetic testing (PGT) cycles found that the PPOS group had a lower cumulative live birth rate, 28.4% vs. 40.7% (P=0.004), and an adjusted odds ratio of 0.556 (95% CI 0.377–0.822); the number of high-quality blastocysts was also lower, 2.82±2.83 vs. 3.20±2.79 (P=0.032). No significant differences were found between polycystic ovary syndrome and low response subgroups. [3]
Both groups in this cohort had frozen embryos, which reduces the impact of different transfer strategies. However, there are still treatment options and other confounding factors that cannot be used to confirm that PPOS leads to a decrease in live birth rates. It cannot be directly regarded as two conflicting conclusions with the aforementioned summary results of first-time transfer live birth rates - the populations, designs, and endpoints of the two are different.
POSEIDON low prognosis group
A retrospective cohort of 1329 persons compared PPOS (734 persons) with a flexible antagonist regimen (595 persons). After grouping by POSEIDON, no significant differences were found in the cumulative live birth rate among the four groups; there were also no significant differences in the number of retrieved eggs, normal fertilized eggs, and number of available embryos in groups 3 and 4. [4]
The average number of eggs retrieved was 2.8 vs. 2.8 in Group 3 and 1.6 vs. 1.6 in Group 4 in the study. The same mean after rounding does not mean that all patients have the same response, nor does it prove that dressing change is of no value. The time to live birth was shorter in antagonist group 1, 10.4 ± 3.3 months versus 13.1 ± 4.4 months; the transfer strategies differed between the two groups, and this should be taken into account when interpreting. [4]
Comparison with microstimulation
Another review included 14 retrospective studies, involving 4182 women with reduced reserves, comparing PPOS with microstimulation regimens of clomiphene or letrozole plus gonadotropins. The PPOS group had fewer premature LH peaks (OR 0.10, 95% CI 0.07–0.15), lower cycle cancellation rate (OR 0.78, 95% CI 0.64–0.95), higher quality embryo rate and cumulative pregnancy rate; the difference in the number of retrieved eggs was not statistically significant (P=0.08). The number of ovarian stimulation days and the total amount of gonadotropin increased. [5]
Luteal phase and follicular phase stimulation
A systematic review published in 2026 included 5 studies and 312 low responders, including 114 in the luteal phase group and 198 in the follicular phase group. The difference in the number of retrieved eggs did not reach statistical significance; the number of embryos on day 3 was higher in the luteal phase group, with a mean difference of 0.77 (95% CI 0.29–1.25); there was no significant difference in clinical pregnancy rate, RR 1.26 (95% CI 0.78–2.02). The luteal phase group took longer for ovarian stimulation. [6]
Included studies included randomized trials and observational studies with low to very low certainty in evidence and did not provide pooled results sufficient to determine differences in live births. It supports that luteal phase stimulation can obtain usable oocytes and embryos, but is not sufficient to establish non-inferiority to conventional follicular phase stimulation, let alone demonstrate a live birth benefit.
Double stimulation vs. two regular stimulations
A 2018 multicenter observational study included 310 patients with poor prognosis. When only considering follicular phase stimulation, 42.3% of patients obtained at least one euploid blastocyst; when the results of subsequent luteal phase stimulation were added together, the proportion was 65.5%. Fertilization rates, blastocyst formation rates and euploidy rates were similar between the two stimulations. [7]
The comparison here is between "one egg retrieval" and "the cumulative results after adding a second egg retrieval". It shows that a second egg retrieval can bring new opportunities, but it cannot answer whether doing it twice in the same cycle is better than doing it twice across two cycles.
The 2023 BISTIM trial randomized 88 low responders to directly compare dual stimulation with two conventional antagonist cycles. The cumulative number of retrieved eggs in the double stimulation group was 5.0±3.4, and that in the control group was 4.6±3.4. The difference was not statistically significant (P=0.56). The numbers of available embryos were 0.9±1.1 and 1.5±1.1 respectively, which were fewer in the dual-stimulation group; the cumulative live birth rate was 17.9% vs. 34.1%. The difference did not reach statistical significance, and the trial did not provide sufficient statistical power for comparison of live birth rates. [8]
The actual comparison objects of the two studies are different
| Research | actual comparison | understanding that can be supported |
|---|---|---|
| 2018 observational study 310 people, multicenter | Cumulative results after one follicular phase stimulation and additional luteal phase stimulation | Adding one more egg retrieval can increase the chance of obtaining euploid blastocysts [7] |
| BISTIM randomized trial 88 people | Double stimulation, two egg retrievals, and two regular cycles, two egg retrievals | It has not been proven that dual stimulation increases the cumulative number of eggs retrieved; completing the second egg retrieval faster does not mean faster live birth [8] |
ESHRE allows the use of dual stimulation when fresh embryo transfer is not planned and the accumulation of eggs or embryos is the goal, and also lists it as an arrangement that can be considered for emergency fertility preservation. Recommendation does not mean that it can improve the quality of eggs per unit, nor does it mean that all patients with low reserves need dual stimulation. [1]
Safety and offspring data
A single-center retrospective cohort included 16,493 infants born between September 2013 and July 2021, including 15,245 in the PPOS group and 1,248 in the antagonist group. The study did not observe an increase in the rate of congenital malformations in the PPOS group, and there were no significant differences in multiple birth and neonatal indicators between the two groups. [9]
This is a large-scale observational study, but the numbers of the two groups are quite different, and the results are limited by the retrospective design and selection of study subjects. Follow-up mainly involves the birth and neonatal period, and there is no guarantee that all outcomes will be the same throughout childhood or even adulthood. The existing data generally provide support for neonatal safety, and long-term follow-up is still necessary.
In a 2026 review of randomized trials, 10 studies comparing PPOS with antagonists reported no moderate to severe ovarian hyperstimulation syndrome (OHSS) events. No cases were observed in the sample, which does not mean the risk is zero. [2]
A freeze-all strategy removes the risk that a pregnancy from that transfer will worsen OHSS, but it cannot eliminate all risks related to ovarian stimulation and triggering. For high responders, the gonadotropin dose, trigger method, transfer strategy, and the possibility of simultaneous natural conception need to be evaluated at the same time. PPOS cannot be regarded as the same safe combination as an antagonist plus an agonist trigger solely because it uses oral medication with freeze-all. [1]
The real cost of cryopreservation
Modern vitrification technology has a higher overall survival after warming, but the oocytes or embryos may still be unusable after freezing and thawing. The results vary from different laboratories, developmental stages and frozen subjects, and a certain blastocyst survival after warming cannot be applied to all eggs or embryos; survival after warming is not equal to implantation or live birth.
A cryopreservation strategy adds freezing, storage, warming and a later transfer, often delaying the first transfer, but the specific waiting time is determined by recovery status, cycle preparation, and clinic schedule. For people who could have had fresh embryos transferred, there needs to be a practical reason for whether to freeze them entirely.
Population Selection and Treatment Burden
Put the plan back into context, along with cost, time and schedule of visits.
Key points for discussion in different situations
The following table is used to understand the situations in which each protocol may be considered. The specific drugs, initiation timing and transfer arrangements will be determined by the attending doctor based on complete information. "Discussable" in the table is a communication option, not a personal prescription.
Situation and Discussable Arrangements
| situation | Arrangements that can be discussed | Trade-offs that need explanation |
|---|---|---|
| The ovarian reserve is normal and I hope to have a transfer this cycle. | Possible conventional stimulation regimen for preservation of fresh embryo transfer | The PPOS compared in this article usually do not include fresh embryo transfer in the stimulated patient; eligibility for fresh embryo transfer still require clinical evaluation |
| It has been determined to use a freeze-all strategy or undergo PGT | Options such as PPOS or antagonists can be discussed | An existing freeze-all plan reduces the additional process difference introduced by PPOS; efficacy cannot be generalized |
| PCOS or expected high response | Guidelines support antagonist regimen; combine risk assessment of agonist triggers with freeze-all | It is necessary to prevent OHSS as a whole, and freeze-all cannot be regarded as zero risk. |
| POSEIDON Group 1 and 2 Normal indicators but poor response in the past | Review previous response, medications, and egg retrieval process, and then discuss adjustments | The time difference between individual cohorts is not sufficient to prescribe a single priority for both subgroups |
| POSEIDON Group 3 and 4 Reserve index is low | PPOS, antagonists and other arrangements suitable for the individual can be discussed | Low reserves do not automatically exclude fresh embryo transfer, nor do they automatically require embryos to be saved first; time and cost need to be assessed [15] |
| Previous early LH surge or early ovulation | Verify the nature of the event, timing of dosing, compliance and monitoring, and then discuss premature LH-surge suppression strategies | Progesterone options can be discussed, but there is no guarantee that it will not happen again, nor can cause analysis be skipped |
| Medical treatment in other places or across borders | Make arrangements for ultrasound, necessary blood drawing, follow-up consultation and egg retrieval in advance | Oral premature LH-surge suppression can reduce related injections, but it does not mean that it can reduce the required monitoring. |
| Time-critical situations such as before tumor treatment | Start randomly, consider dual stimulation if necessary | Need to coordinate with the treatment time limit of the original disease; usually for the purpose of cryopreservation of eggs or embryos |
| It is possible to conceive naturally during this cycle | Explain and evaluate with the doctor before the cycle begins | Guidelines for luteal-phase start include no possibility of spontaneous conception; random initiation also needs to address this risk |
Cost, time and visit burden
Oral progestins are generally less expensive than antagonist injections, but LH-surge suppression drugs are only part of the total cost. Gonadotropins, monitoring, egg retrieval, cryopreservation, warming and subsequent transfer should be compared together, including travel and accommodation costs if necessary.
Process differences betweenantagonist regimen and PPOS
| Compare items | GnRH antagonist regimen | PPOS protocol |
|---|---|---|
| LH-surge suppression drug administration | Commonly used is daily subcutaneous injection, with fixed and flexible starting methods. | Commonly used is oral progesterone, and there are different drugs and activation methods. |
| Peak suppressor drug prices | Usually higher, varies by region and product | Usually lower, does not mean the entire course of treatment is necessarily cheaper |
| Gonadotropin dosage | Determined by population, drugs and stimulation strategies | It cannot be generally concluded that there must be more; it needs to be compared directly with similar groups of people. |
| Monitor | Arrange ultrasound and necessary hormone examinations based on follicle development and risk | Monitoring is also required; oral premature LH-surge suppression does not replace observation of follicular response |
| My own fresh embryo transfer | May remain possible, ultimately depending on clinical conditions | Usually not scheduled; use available embryo freezing or egg freezing strategies |
| Trigger mode | Select by response, OHSS risk, and transfer plan | Corresponding trigger strategies can also be adopted; trigger risks cannot be ignored just because of oral premature LH-surge suppression. |
| first transfer time | If fresh embryo transfer is suitable, it can be performed in the same cycle after egg retrieval. | Arrange for a subsequent frozen embryo transfer cycle; those who freeze eggs need to plan for fertilization and transfer separately |
| Total cost and time | Need to estimate according to the complete process | Freezing, preservation, warming and subsequent transfer need to be taken into account. You cannot just compare the unit price of peak suppressing drugs. |
Only antagonists and PPOS are compared in the table. luteal-phase start is not a unified dosing regimen and therefore is not combined with PPOS. Reference [4] did not do a complete cost analysis; its shorter time to live birth in Group 1 cannot be taken as a promise that every patient on an antagonist will deliver the same month earlier. [4]
If freeze-all is already established because of PGT, endometrium problems, or other reasons, the additional transfer delay associated with PPOS may be smaller. There remains a need to compare actual drug responses, past outcomes, freezing schedules, and monitoring arrangements that can be accomplished.
Choices when ovarian reserve is significantly reduced
A persistently low antral follicle count, anti-Müllerian hormone near the lower limit of detection, and multiple previous egg retrievals of only 0 to 2 eggs suggest the need for careful evaluation of expected response. Reserve indicators, ovarian stimulation response and whether transfer is possible are different issues, and one indicator cannot be used to replace all judgments.
Decreased reserves, low response, and POI
Diminished ovarian reserve describes a decrease in the number of available follicles; ovarian hyporesponsiveness describes the response to stimulation or egg retrieval results; POSEIDON uses age, reserve, and past response to stratify prognosis. The three are related and have different meanings.
Premature ovarian insufficiency (POI) refers to impaired ovarian activity before the age of 40 years. Current joint guidelines include at least 4 months of spontaneous amenorrhea or menstrual irregularity and FSH >25 IU/L; further evaluation is required when diagnostic uncertainty exists. It does not require that menstruation has permanently stopped; some patients may still have intermittent ovarian activity. Low AMH by itself is not a substitute for POI diagnosis. [13]
Antral follicle count can only help predict
Medications that stimulate ovulation do not replenish the resting follicle pool. Antral follicle count can help estimate response to stimulation, but it is an ultrasound count at a specific time point and is not a strict upper limit on the final number of eggs retrieved. Low antral follicle count or low AMH also do not alone accurately predict egg quality, individual chances of live birth, or serve as the sole basis for refusing treatment. [12]
In the low-responder subgroup of the 865-case cohort, the adjusted odds ratio for cumulative live birth rate between regimens was 2.126, with a 95% confidence interval extending from 0.454 to 9.965. A wide range indicates that the estimate is imprecise and unsuitable for promising that either side is better. For an individual, why the previous cycle failed is often more worth investigating than simply changing the name of a plan. [3]
Treatment goals and assessment time points
When there are very few eggs retrieved in a single cycle, the records of multiple treatments can be viewed together, including the number of mature eggs, the number of available embryos, whether the transfer has been completed, and the cumulative live birth outcome. However, "accumulate first and then transfer" is not the default arrangement for all patients with low reserves: if there are already available embryos, the endometrium is suitable, and there are no other restrictions, you should work with your doctor to evaluate the benefits and burdens of transferring now and continuing to retrieve eggs. [4][15]
Aspects that can be actually adjusted
01 Discuss launch arrangements when there is clear time pressure
random start, luteal phase priming, or dual stimulation can reduce some of the waiting, but faster egg retrieval the second time does not mean a shorter time to live birth. If a transfer that could have been performed was postponed for the sake of accumulation, this time should also be included. [1][8]
02 Reduce unnecessary cancellations by reason
Premature ovulation, follicular asynchrony, insufficient response, abnormal trigger response and failure to retrieve eggs require different verifications. Even if there are only one or two follicles expected, the reason for cancellation should be confirmed first and then discuss how to adjust for the next cycle. The proportion of LH elevation in the normal reserve test cannot be directly used as the probability of early ovulation in patients with low reserve. [11]
03 Limit dosage discussion to evidence
ESHRE does not recommend gonadotropin doses higher than 300 IU/day for expected poor responders, which is a strong recommendation, but the certainty of the evidence is very low. This recommendation does not mean that increasing the dose will never change the number of eggs retrieved under any circumstances. It suggests that ultra-high doses should not be used as a routine method to improve low response. [1]
auxiliary medication
Adjuvant medication and ESHRE 2025 opinions in low-responsive people
| auxiliary medication | ESHRE 2025 Comments on Low Responders | Evidence certainty |
|---|---|---|
| growth hormone | May not be recommended for use before or during stimulation Conditionally recommended | Very low[1] |
| Dehydroepiandrosterone (DHEA) | Not recommended for use before or during stimulation. Strong recommendation. | Low[1] |
| Testosterone pretreatment | May not be recommended for use before stimulation. Conditionally recommended. | Medium[1] |
It is recommended that clinically important outcomes, evidence credibility, and treatment burden should also be considered. It cannot be understood that every study has obtained the same results. If the clinic proposes these adjuvant medications, it can confirm what type of research the basis is from, what endpoints are expected to improve, what risks and costs are involved, and how to reassess if no response is seen. Its inclusion in individualized attempts does not mean that it has been proven to improve individual live birth rates.
When no usable embryos are obtained for multiple consecutive cycles, when there is persistent no follicular response, or when the burden of treatment becomes unbearable, the scope of discussion can be expanded proactively. Whether to continue autologous egg therapy and whether and when to discuss egg donation should be decided jointly by the patient and doctor. Egg donation is also affected by local laws, accessibility and parental rights arrangements, and cross-border situations need to be verified separately.
Medical treatment communication and cycle records
The only things that can be taken away are the records, not the protocol names.
Differences in practices among different centers
The same information may receive different recommendations in different centers. Differences can arise from commonly used transfer strategies, drug availability, judgment of evidence, laboratory experience, and patient scheduling, or they may reflect incomplete information about prior treatment. When comparing clinics, ask your doctor for specific reasons.
Centers where fresh embryo transfer is a common arrangement will pay more attention to retaining the opportunity for transfer in the current cycle; procedures that have originally planned frozen or PGT are more likely to be included in PPOS. The guideline retains the premise of full freezing of PPOS, and the certainty of the evidence is not high, so the degree of adoption may vary among centers. [1]
Among the data cited in this article, some of the PPOS cohorts are from a single center in China and the grouping is non-random, and there are also randomized trials. Geography cannot be used as a surrogate for the quality of evidence. This judgment should look at the study design, sample, population, endpoints, and risk of bias.
When changing centers or cross-border medical treatment, it is more useful to bring all previous medications, ultrasounds, hormones, triggers and laboratory records than just telling the doctor that "you have done such and such a program." Just because the drug has the same name does not mean that the initiation time, dosage, and transfer strategy are also the same.
Consultation and record keeping
01 Why choose this start day for this cycle, whether it involves the luteal phase or random start.
02 What medicine should be used to prevent premature LH surge, whether to use fixed or flexible start, and how to contact the clinic after missing a dose or injection.
03 Whether to retain the opportunity for fresh embryo transfer; if it is planned to freeze them, what are the specific reasons?
04 If subsequent frozen embryo transfer is required, when is expected to evaluate the endometrium, and how will the waiting time and cost be calculated?
05 What is the starting dose of gonadotropin? If low response is expected and it is planned to use more than 300 IU/day, what is the basis and expected benefit?
06 Which monitoring must be completed on time, whether off-site examinations can be accepted by the center, and what situations require early return for consultation.
07 What was the reason for the failure to meet expectations in the previous cycle, and which link was specifically adjusted this time.
08 Whether there are already transferable embryos, what are the considerations for immediate transfer and continued accumulation?
09 When to re-evaluate treatment goals, and what results will be used to determine whether to continue.
These questions are intended to support adequate communication and are not intended to be used to make self-initiated changes to medications, dosages, monitoring dates, or trigger times.
Records to be kept for each cycle
cycle record table
| Project | Record content |
|---|---|
| Baseline and Startup | Menstrual date or ovulation date, initiation day, antral follicle count, basal hormones, anti-Mullerian hormone and test date; progesterone at initiation, necessary pregnancy exclusion information |
| ovulation-stimulating medication | Drug name, starting dose, gradual adjustment, total number of days and total dosage |
| premature LH-surge suppression arrangement | Drug name, start date, dosage and administration method; if a dose or dose is missed, record the time and clinic’s handling opinions |
| Monitor | The number and diameter of follicles, endometrium condition, corresponding date and hormone results of each ultrasound |
| trigger | Drug name, dosage, accurate administration time and related test results |
| Egg retrieval and fertilization | Egg retrieval time, number of eggs retrieved, number of mature eggs, fertilization method and normal number of fertilizations |
| embryonic development | Number of embryos on day 3, number of blastocysts, number of available embryos, freezing stage and quantity |
| genetic testing | If doing PGT, keep the test type, number of tests submitted, complete report and genetic counseling opinions |
| transfer and follow-up | Fresh or frozen embryos, transfer date, stage and number, pregnancy and live birth outcomes |
| Incomplete stages | Date of cancellation or interruption, which step you stopped at, reasons confirmed by the doctor and suggestions for next time |
Keywords Fertility stimulation regimen · GnRH antagonist · PPOS · luteal-phase start · random start · Double stimulation · freeze-all · Premature LH surge · POSEIDON stratification · Decreased ovarian reserve · Premature ovarian insufficiency
Evidence appendix
The source, scale and interpretation limitations of each data in thetext are listed in the table below.
Applicable scope of key evidence
| Literature | research and scale | Information used in this article | Interpretation limitations |
|---|---|---|---|
| [1] | ESHRE 2025 Update Guide | premature LH-surge suppression plan, stimulation timing, trigger, low-reaction dose and auxiliary medication | Each recommendation has independent conditions; strength of recommendation does not equal certainty of evidence |
| [2] | 20 randomized controlled trials, 4430 people | Live birth outcomes and number of eggs retrieved in first transfer compared with PPOS and antagonists | None had an overall low risk of bias; not generalized to superiority to all endpoints or to all populations; no significant difference in cancellation rate and early onset LH surge |
| [3] | Retrospective cohort, 865 PGT cycles | The cumulative live birth rate of PPOS in the normal response subgroup was lower. | Non-randomized, single center; only 82 people in the low-response subgroup, estimated imprecisely |
| [4] | Retrospective cohort, 1329 individuals | No significant differences in cumulative live birth rates were seen between POSEIDON groups | Equivalence cannot be proven; the transfer strategies of the two groups are different; no cost analysis has been done |
| [5] | 14 retrospective studies, 4182 people | Results such as LH peak and cancellation rate of PPOS relative to minimal stimulation | Control is not an antagonist; cumulative pregnancy rate does not equal cumulative live birth rate |
| [6] | 5 studies, 312 people | Egg retrieval and embryonic development results of luteal phase stimulation | Evidence is low to very low; lack of adequate live birth outcomes, non-inferiority not established |
| [7] | Multicenter observational study, 310 people | Increased chance of cumulative euploid blastocysts after luteal phase stimulation | Compares "once" to "twice"; does not replace a random comparison of two versus two |
| [8] | BISTIM randomized trial, 88 people | Double stimulation does not show a cumulative advantage in egg retrieval, and the second egg retrieval is faster | Failure to provide sufficient power for comparison of live birth rates; specific egg freezing and embryo freezing process and impact of withdrawal |
| [9] | Retrospective cohort, 16,493 infants | No significant differences were found in multiple neonatal outcomes | Single center, huge disparity in numbers between two groups; cannot represent long-term offspring outcomes |
| [10] | Continuous ultrasound observation of healthy women | Multiple batches of follicular growth waves in the same menstrual cycle | Physiological observation does not mean that specific treatment will increase the live birth rate |
| [11] | Open-label randomized controlled trial, 348 people | Cumulative live birth rate and LH elevation results | Two complete processes were compared; there was no early ovulation in either group. |
| [12]–[15] | Professional opinions, joint guidelines and clinical studies [15] is an 838-person multicenter randomized trial | Interpretation of antral follicle count, POI diagnosis, random initiation; 32% whole frozen versus 40% fresh embryos in low prognosis population (RR 0.79, 95% CI 0.65–0.94) | Each source has a defined scope and they cannot substitute for one another as evidence of LH-surge suppression efficacy; [15] compares transfer strategies, not LH-surge suppression medication. |
References
[1] Ata B, Bosch E, Broer S, et al.; ESHRE Guideline Group on Ovarian Stimulation. ESHRE guideline: ovarian stimulation for IVF/ICSI: an update in 2025. Hum Reprod. 2026;41(4):498–514. doi:10.1093/humrep/deag018
[2] Martins WP, Nastri CO. Progestogen-primed ovarian stimulation vs GnRH antagonists and/or agonists for women undergoing assisted reproduction: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2026;68(2):188–201. doi:10.1002/uog.70267
[3] Zhou R, Dong M, Huang L, et al. Comparison of cumulative live birth rates between progestin-primed ovarian stimulation protocol and gonadotropin-releasing hormone antagonist protocol in different populations. Front Endocrinol. 2023;14:1117513. doi:10.3389/fendo.2023.1117513
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medical statement
This article is for health education and doctor-patient communication and cannot replace specialist consultations in reproductive medicine. The research results in this article describe group situations and cannot be directly converted into individual success rates. The laboratories, protocols and charges of each center are different, and the specific treatment is determined by the attending doctor based on complete information.
The timing of starting ovarian stimulation, drugs and dosage, monitoring, triggering, egg retrieval and transfer arrangements are all medical decisions. The guideline dosage thresholds appearing in this article are only for interpretation of evidence and do not constitute a prescription. Please do not add or subtract medicines or adjust medical treatment based on them.
If you experience significantly increased abdominal distension, decreased urine output, significant short-term weight gain, labored breathing, fever or severe abdominal pain after ovarian stimulation or egg retrieval, please contact the medical institution in time; if symptoms are serious, seek medical attention immediately.
Turn a protocol name into questions that can be checked
FS can help organize previous cycles, records from different clinics and the treatment pathway. Medication, dose, monitoring, trigger and transfer remain clinical decisions for the treating physician.
Guidelines and research
The article preserves populations, endpoints, effect estimates and certainty of evidence. Guidance changes; the treating clinician should confirm it before treatment decisions.
- ESHRE ovarian stimulation guideline 2025
- Systematic review of PPOS versus GnRH protocols (2026)
- Cumulative live birth after PPOS and antagonist protocols
- POSEIDON low-prognosis cohort
- Systematic review in diminished ovarian reserve
- Luteal versus follicular stimulation review
- Multicentre DuoStim study
- BISTIM randomized trial
- Neonatal outcomes after PPOS
- Ovarian follicular-wave study
- Randomized trial in women with normal reserve
- ASRM ovarian-reserve testing opinion
- Evidence-based POI guideline
- Random-start stimulation study
- Fresh versus frozen transfer in women with low prognosis
This article is for health education and clinical discussion. It is not a diagnosis or prescription and does not replace consultation with a reproductive-medicine specialist.