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In vitro maturation: a committee opinion (2021)


The results of in vitro maturation (IVM) investigations suggest the potential for wider clinical application. This document discusses the efficacy of IVM as reported in the published literature to date. 
 
In vitro fertilization (IVF) typically involves ovarian stimulation with the use of exogenous gonadotropins to induce the maturation of gonadotropin-sensitive follicles and inhibit the atresia of nondominant folicles (1, 2). The classic use of the term in vitro maturation (IVM) refers to the maturation of immature cumulus-oocyte complexes (COCs) in culture from prophase I (i.e., from the germinal vesicle [GV] stage) through meiosis I to reach metaphase II (MII) after their recovery from follicles that have not been exposed to the preovulatory trigger (3). This was defined largely in nonhuman animal studies. In clinical human IVF, however, the term IVM is often used to refer to in vitro maturation of oocytes retrieved at the GV or metaphase I (MI) stage from follicles after exposure to exogenous FSH and/or hCG (‘‘follicle priming’’) to increase the likelihood of obtaining some mature oocytes (4, 5). Interpretation of studies reported in the literature could be clarified if specific terminology was used to delineate between IVM with and without short gonadotropin stimulation, and with and without hCG exposure before retrieval (6, 7).

Table 1. Definitions of IVM (3, 8-11)

Term in literature Oocyte maturation Exposure to hormones Reference
Biological definition of IVM
 

 

 

 

 
GV to MII No exposter to hCG or LH Edwards 1965 (3)
Variations on Definition of IVM 
Truncated IVF without FSH GV oir MI to MII HCG primes intermediate follicles, no FSH Chian 1999 (8)

Follicle priming with FSH GV oir MI to MII Minimal FSH stimulation, no HCG Wynn 1998 (9)
Mild stimulation IVF/Truncated IVF GV oir MI to MII Minimal FSH stimulation and early HCG administration to prime intermediate follicles Fadini 2009 (10)
Rescue IVM Any immature oocytes at retrieval to MII Controlled ovarian hyperstimulation cycle resulting in GV or MI oocytes, denuded of cumulus cells Sacha 2018 (11)

IVM=in vitro maturation; GV=germinal vesicle; MII=metaphase II; hCG=human chorionic gonadotropin; FSH=follicle-stimulating hormone; LH= luteinizing hormone; MI=metaphase I
The human oocyte reaches its full size (~100–120 mm in diameter) at the small antral stage, during which time the follicular diameter is only a fraction of its final ovulatory diameter. The ability of an oocyte to resume and complete meiosis is closely linked to follicular diameter (12–15). In humans, the kinetics of oocyte maturation have been studied with the use of oocytes obtained from oophorectomy specimens from non-malignant gynecologic disorders and then cultured to undergo IVM, reaching MII after 36–48 hours (3). 
 
It should be noted that even if an immature oocyte progresses to the MII stage with the use of IVM (i.e., completes nuclear maturation), it may not necessarily have undergone cytoplasmic maturation and achieved full developmental competence. For a mature oocyte to undergo successful fertilization and subsequent development, synchronization of nuclear and cytoplasmic maturation must occur (16). Nuclear maturation consists of GV breakdown induced by the LH surge followed by resumption of meiosis and extrusion of the first polar body (MII) (3). Cytoplasmic maturation refers to an accumulation of factors that prepare the cytoplasm for fertilization and embryonic development (17, 18). Epigenetic processes are a component of nuclear and cytoplasmic oocyte maturation, influencing development after fertilization (19, 20). For this reason, the potential for epigenetic disruption, such as abnormal methylation of maternally expressed genes, warrants careful evaluation in oocytes matured in vitro (21).  

POTENTIAL APPLICATIONS OF IVM 

The clinical application of IVM may be limited by alternative evidence-based strategies to successfully mitigate the risk of ovarian hyperstimulation syndrome (OHSS) in high-risk populations. Historically, candidates for IVM have included those at risk for OHSS, including women with polycystic ovary syndrome (PCOS) or polycystic ovary (PCO)–like ovaries and women with estrogen-sensitive cancers. Because significantly less medication is used for stimulation with the use of IVM, and the stimulation is of shorter duration requiring fewer injections and less monitoring, the financial and emotional burden is reduced compared with traditional IVF cycles. In addition, patients with limited time before potentially gonadotoxic cancer treatments may be candidates to use IVM for fertility preservation (22, 23). Finally, a study has shown the effectiveness of IVM in patients with repeated assisted reproduction failure due to resistant ovary syndrome (24).  

IVM IN CLINICAL PRACTICE 

Follicular Priming 

There have been several clinical studies comparing IVM with conventional IVF using in vitro matured human oocytes in PCO-like and PCOS patients (25–29) and in ovulatory women (26, 30, 31). Several trials have also evaluated the utility of follicular priming versus the retrieval of oocytes from unstimulated antral follicles (10, 25). Three methods of follicular priming have been reported. One method is to minimally stimulate ovaries with low doses of FSH for 3–6 days, followed by retrieval on cycle day 7–10 in the absence of hCG administration. Other approaches use only hCG (single 10,000 IU injection) to ‘‘prime’’ intermediate-sized follicles 36 hours before oocyte retrieval, as well as the addition of minimal FSH stimulation before this hCG priming. This form of priming with hCG is physiologically different than late follicular administration of hCG in a traditional IVF cycle. Priming with FSH and a single priming injection of hCG on cycle day 6, followed by IVM, in 921 PCOS women resulted in a cumulative live birth rate per cycle of 33.7% (32). A retrospective cohort study comparing IVM with the use of FSH and an hCG priming injection versus conventional IVF in 919 women with high antral follicle count (AFC) reported that although the number of mature oocytes and good-quality embryos was lower in the IVM group, the cumulative live birth rate after one cycle of IVM was 239/608 (39.3%) versus 
155/311 (49.8%) for IVF (29). 
 
The combination of gonadotropin and hCG priming compared with single-agent follicular priming has been studied with disparate results. A large randomized trial in 400 women with normal ovaries showed that when both FSH and hCG were used for priming, the percentage of oocytes that matured in vitro and the total number of available mature oocytes was improved, although 20% of recovered oocytes were matured in vivo in this treatment group. Clinical pregnancy rates after fresh embryo transfer were highest when both FSH and hCG were used, 26.5%, compared with 11.8%, 5.4%, and 13.7% in the nonprimed, hCG-primed, and FSH-primed groups, respectively (10). However, embryos in this group likely arose from a combination of both in vivo and in vitro matured oocytes, complicating interpretation of these results. 
 
In several studies from Belgium in which IVM was conducted after a short (3-day) FSH stimulation with no hCG, clinical pregnancy rates have been reported. In a small study of 39 PCO/PCOS patients and 73 IVM cycles, after vitrified-warmed embryo transfer, the ongoing clinical pregnancy rate per transfer was 7/22 (31.8%) (33). A larger study of 121 patients and 239 IVM cycles in which 3 days of FSH and no hCG was administered and oocytes were retrieved from follicles no larger than 6 mm, an ongoing clinical pregnancy rate of 9/24 (37.5%) after vitrified-warmed embryo transfer was reported (34). Pregnancy rate after fresh embryo transfer was significantly lower in both of these studies. 
 
Subsequently, a ‘‘freeze-all’’ IVM strategy was used in a study of 79 PCOS patients, resulting in a cumulative live birth rate per patient of 17/78 (21.8%) (35). Further supporting the notion that freeze-all strategies are better for FSH priming of IVM cycles, a recent study showed a very high miscarriage rate after IVM when fresh transfers were compared with frozen-thawed embryo transfers (36.8% vs. 4.5%) (28). One thing to bear in mind with all of these studies is that there is a high level of attrition from retrieved immature COCs to good-quality blastocysts, owing in part to low maturation success after IVM. The chance of a single immature oocyte resulting in a live birth was only 1.1% (35). In addition, interpretation of these studies is complicated not only by significant variation in the stimulation protocols used, but also by inconsistent reporting of the stage of meiotic maturation of the oocytes at retrieval (GV vs. MI, as well as any mature MII oocytes recovered). 

In Vitro Maturation and Cancer 

IVM could be beneficial for patients desiring fertility preservation because of impending gonadotoxic cancer treatment (36). In one study, 248 breast cancer patients, aged 18–40 years, awaiting neoadjuvant chemotherapy were candidates for oocyte vitrification following IVM, at either the follicular or the luteal phase of the cycle (36). No major differences were seen in the number of oocytes retrieved or their IVM rates, whatever the phase of the cycle at which oocyte retrieval was performed, indicating that this novel use of IVM is clinically useful. 
 
However, another study showed that vitrified-thawed IVM oocytes had a low survival rate (59.8%), lower fertilization and cleavage rates, and significantly lower pregnancy (10.7% vs. 36.1%) and take-home baby (8.9% vs. 25.9%) rates compared with fresh IVM oocytes (37). The authors concluded that the reproductive potential of vitrified IVM oocytes is impaired owing to the vitrification-warming procedure. Similarly, another study showed very poor pregnancy and delivery outcomes from vitrified-thawed embryos derived from IVM oocytes for cancer patients (38). 
 
Moreover, IVM of oocytes after recovery from thawed ovarian tissue frozen from postmenarchal versus premenarchal girls yielded a low rate of maturity in both groups (28.2% vs. 15.5%, respectively), which was further reduced in girls under 5 years of age (4.9%) (39). Collectively, these studies highlight the need for more research targeting improvement of IVM media, as well as IVM protocols for pre-menarchal girls. Recent studies have shown that using antimullerian hormone level and AFC information can help physicians to more accurately counsel patients on the potential likelihood of successful fertility preservation with the use of this approach (40, 41).  

Oocyte Retrieval and Culture 

There are no established criteria to identify the ideal timing or method for oocyte retrieval, with most studies using a lead follicular diameter of up to 10 mm (31, 42). Lead follicle diameters greater than 13 mm have been associated with reduced numbers of oocytes collected and matured (43), possibly related to subsequent atresia of the nondominant follicles from withdrawal of endogenous FSH support. Some protocols 
require an endometrial thickness of >5 mm while others do not include endometrial thickness as a criterion. 
 
The aspiration technique differs for immature oocytes compared with mature oocytes retrieved in traditional IVF owing to the lack of cumulus cell expansion and tighter adherence of the immature oocyte to the follicle wall. Double-lumen needles to flush follicles have been described but do not appear to be necessary to retrieve immature oocytes (44). The optimal aspiration pressure and needle design have yet to be determined, with negative pressures ranging from 80 to 120 mm Hg and needle sizes ranging from 16 to 20 gauge (9, 31). Extremely high aspiration pressure has been shown to strip the oocyte of cumulus cells and negatively affect maturation and oocyte competence (45). 
 
There is no consensus on the medium formulation that is best suited for IVM. Media typically simulate tissue culturemedium, composed of high levels of glucose and normal levels of pyruvic and lactic acids, along with essential and nonessential amino acids and frequently supplemented with FSH and hCG/LH. Several versions are available commercially. A few studies on the improvement of IVM medium for human oocytes have been reported, but significantly more research is needed in this area. 
 
A recent development in IVM is the inclusion of a prematuration (pre-IVM) step. Some commercial IVM media have historically included a short (2 hour) preincubation step before moving the eggs into the IVM medium. However, pre-IVM medium contains reagents, such as forskolin, and/ or C-type natriuretic peptide, to block meiotic resumption and maintain oocytes at the GV stage for up to 24 hours until they are moved into IVM medium. This strategy is designed to better support oocyte cytoplasmic maturation and improve oocyte competence after IVM. The first report of human IVM including this pre-IVM step and improved IVM medium containing amphiregulin and FSH reported an increase in oocyte maturation after IVM, as well as an increase in good-quality blastocysts (46). 
 
Chromosome constitution, and DNA methylation and expression of imprinted genes, in embryos generated after pre-IVM/IVM appear to be normal (47, 48). A randomized controlled trial examined the effectiveness of pre-IVM versus standard IVM, defined as a short FSH stimulation without hCG administration. Results from that study suggested that in women with high AFC, those in the pre-IVM group had significantly higher maturation and clinical pregnancy rates, but both groups had similar live birth rates and neonatal outcomes (48).  

Fertilization 

In a randomized control trial of standard insemination versus intracytoplasmic sperm injection (ICSI) for sibling IVM oocytes from patients with PCOS, there was no difference reported for all outcomes measured, including fertilization rates and blastocyst development (49). Although IVF can readily be used to fertilize IVM oocytes, ICSI has been advocated as the preferred method. However, although fertilization rates appear to be increased with the use of ICSI for IVM oocytes, developmental competence may be impaired, as demonstrated in one comparative trial (27). 
 
The fertilization success rate of matured oocytes in patients who did not receive gonadotropins was only 37.7% (229/608 matured oocytes) with the use of conventional IVF compared with 69.3% (318/459 mature oocytes) when ICSI was used. Despite lower fertilization results, the implantation rate was significantly higher in embryos derived from oocytes fertilized with the use of conventional IVF versus ICSI (24.2% vs. 14.8%; P< .05) as was the clinical pregnancy rates per embryo transfer (34.5% vs. 20.0%; P< .05) (27). However, with the more recent adoption of preimplantation genetic testing for aneuploidies (PGT-A) in many laboratories, ICSI is often the fertilization method of choice. In addition, PGT-A provides some confidence before embryo transfer that IVM-produced embryos are, at minimum, chromosomally normal (50).  

In Vitro Maturation: Safety Concerns 

Scientific studies on the safety of IVM did not demonstrate an increase in imprinting errors after IVM (51), and cellular morphology in IVM oocytes does not differ from in vivo matured oocytes according to transmission electron microscopy (52). The neonatal health and developmental outcome of children conceived with the use of IVM has been studied in small numbers and are thus far reported to be no different than children born through traditional IVF with or without ICSI (53–57). However, the relatively small number of children conceived through IVM compared with IVF limits the accuracy of malformation and anomaly rates, and developmental outcomes cannot yet be adequately assessed.  

SUMMARY 

  • Stimulation protocols with no FSH or short FSH stimulation, followed by hCG priming of intermediate follicles or no hCG, can be successfully used to retrieve oocytes for clinical human IVM. Most recent work in this area has focused on a 3-day stimulation with FSH, with or without hCG administration, and retrieval of oocytes from small follicles. In studies that manipulate the timing of meiotic maturation in vitro to improve oocyte competence, only FSH is used. 
  • A high level of attrition from oocyte to blastocyst is observed in IVM, owing in large part to suboptimal nuclear and cytoplasmic maturation. There is a clear need for more research in this area to increase the efficiency of IVM for clinical application. 
  • The use of ICSI is typically, but not always, combined with the use of IVM. At this time, vitrification of immature oocytes is not recommended owing to reports of poor outcomes. 
  • Because a relatively small number of children have been conceived with the use of IVM, information on the safety of IVM regarding malformation and developmental outcomes cannot yet be fully assessed. However, initial studies are reassuring.  


CONCLUSIONS 

  • Candidates for IVM may include women at risk for OHSS, including women with PCOS or PCO-like ovaries. Efficacy of IVM in the context of estrogen-sensitive cancers, or in women with limited time for initiating fertility preservation before undergoing potentially gonadotoxic cancer treatments, is still not clear. 
  • IVM provides an alternate treatment protocol for these groups of women, with reduced patient burden due to shorter stimulation cycles, fewer injections, and associated reduced drug and monitoring costs. 
  • IVM should be offered by those with expertise gained by specific training, and should always be accompanied by appropriate counseling about expected results and informed consent. This technology is no longer considered experimental. 
  • IVM is not applicable to every patient; only those with a high AFC are good candidates. However, at this time, patients should be made aware that blastocyst conversion is lower and that implantation and pregnancy rates may be reduced compared with conventional IVF. 
  • Large trials comparing clinical outcomes of promising newer methods of IVM versus standard IVF, as well as long-term follow-up studies of neonatal health and developmental outcomes of offspring, are necessary.  

Acknowledgments:
This report was developed under the direction of the Practice Committees of the American Society for Reproductive Medicine (ASRM), Society for Assisted Reproductive Technology (SART), and Society of Reproductive Biologists and Technologists (SRBT) as a service to its members and other practicing clinicians. Although this document reflects appropriate management of a problem encountered in the practice of reproductive medicine, it is not intended to be the only approved standard of practice or to dictate an exclusive course of treatment. Other plans of management may be appropriate, taking into account the needs of the individual patient, available resources, and institutional or clinical practice limitations. The Practice Committees of ASRM, SART, and SRBT and the Board of Directors of the American Society for Reproductive Medicine have approved this report. 
 
This document was reviewed by ASRM members, and their input was considered in the preparation of the final document. The following members of the ASRM Practice Committee participated in the development of this document: Alan Penzias, M.D., Ricardo Azziz, M.D., M.P.H., M.B.A., Kristin Bendikson, M.D., Tommaso Falcone, M.D., Karl Hansen, M.D., Ph.D., Micah Hill, D.O., William Hurd, M.D., M.P.H., Sangita Jindal, Ph.D., Suleena Kalra, M.D., M.S.C.E., Jennifer Mersereau, M.D., Catherine Racowsky, Ph.D., Robert Rebar, M.D., Richard Reindollar, M.D., Chevis N. Shannon, Dr.P.H., M.P.H., M.B.A., Anne Steiner, M.D., M.P.H., Dale Stovall, M.D., Cigdem Tanrikut, M.D., Hugh Taylor, M.D., and Belinda Yauger, M.D. The Practice Committee acknowledges the special contribution of Rebecca Krisher, Ph.D., Ali Ahmady, Ph.D., Robert Gilchrist, D.Sc.Agr. F.S.R.B.; and Johan Smitz, M.D., Ph.D., in the preparation of this document. All Committee members disclosed commercial and financial relationships with manufacturers or distributors of goods or services used to treat patients. Members of the Committee who were found to have conflicts of interest based on the relationships disclosed did not participate in the discussion or development of this document.  

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ASRM Practice Documents have been developed to assist physicians with clinical decisions regarding the care of their patients.
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Current evaluation of amenorrhea: a committee opinion (2024)

Amenorrhea is the absence or abnormal cessation of the menses.
Practice Committee Documents teaser

Inclusive language and environment to welcome lesbian, gay, bisexual, transgender, queer, questioning, intersex, and asexual+ patients (2024)

Creating an inclusive clinical environment to serve lesbian, gay, bisexual, transgender, queer, questioning, intersex, and asexual+ patients is vital.
Practice Committee Documents teaser

Subclinical hypothyroidism in the infertile female population: a guideline (2024)

This guideline reviews the risks and benefits of treating subclinical hypothyroidism in female patients with a history of infertility and miscarriage.
Practice Committee Documents teaser

Tobacco or marijuana use and infertility: a committee opinion (2023)

In the United States, approximately 21% of adults report some form of tobacco use, although 18% report marijuana use.

More Resources

MAC 2021 teaser
ASRM Academy on the Go

ASRM MAC Tool 2021

The ASRM Müllerian Anomaly Classification 2021 (MAC2021) includes cervical and vaginal anomalies and standardize terminology within an interactive tool format.

View the MAC Tool
EMR Phrases teaser
Practice Guidance

EMR Shared Phrases/Template Library

This resource includes phrases shared by ASRM physician members to provide a template for individuals to create their own EMR phrases.

View the library
Practice Committee Documents teaser

ASRM Practice Documents

These guidelines have been developed by the ASRM Practice Committee to assist physicians with clinical decisions regarding the care of their patients.

View ASRM Practice Documents
Ethics Committee teaser

ASRM Ethics Opinions

Ethics Committee Reports are drafted by the members of the ASRM Ethics Committee on the tough ethical dilemmas of reproductive medicine.

View ASRM Ethics Opinions
Coding Corner general teaser
Practice Guidance

Coding Corner Q & A

The Coding Corner Q & A is a list of previously submitted and answered questions from ASRM members about coding. Answers are available to ASRM Members only.

View the Q & A
Covid-19 teaser
Practice Guidance

COVID-19 Resources

A compendium of ASRM resources concerning the Novel Corona virus (SARS-COV-2) and COVID-19.

View the resources
Couple looking at laptop for online patient education materials

Patient Resources

ReproductiveFacts.org provides a wide range of information related to reproductive health and infertility through patient education fact sheets, infographics, videos, and other resources.

View Website

Topic Resources

View more on the topic of in vitro fertilization (IVF)
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Advocacy in Action

Join the ASRM Advocacy in Action 2024 campaign by making a tax-deductible charitable gift before July 31!  Be part of Advocacy in Action
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Order your FREE Vot-ER badge to encourage patients and colleagues to vote!

ASRM) is pleased to announce our partnership with Vot-ER, a grassroots organization dedicated to driving civic engagement among healthcare professionals.

View the Press Release
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Fertility and Sterility On Air - Seminal Article: Ernest Ng, and Zhi Chen

June issue Seminal Contribution: a randomized controlled trial studying the use of progestins for ovulation supression in predicted high responders.  Listen to the Episode
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ASRM Responds to Senate Vote on IVF Bill

ASRM is disappointed that a filibuster prevented the passage of the Right to IVF Act.

View the Press Release
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ASRM Calls for Passage of Family Building Bill

It would increase access to IVF treatments for all Americans, including active-duty service members, veterans, and federal employees.

View the Press Release
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Fertility and Sterility On Air - TOC: May 2024

Topics this month include Iatrogenic and demographic determinants of the national plural birth increase, outcomes between ICSI and IVF with PGT-A. Listen to the Episode
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ASRM publishes IVF one-pagers for media use

The documents lay out the clinical IVF process, summarize oversight of IVF in the U.S., and explain how lawmakers can support access to IVF. 

View the Press Release
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Billing for assisted hatching at biopsy and transfer

We would also like to know if you can bill assisted hatching with biopsy and then assisted hatching again during the transfer cycle. View the Answer
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ASRM Reacts to Cruz/Britt OPED

We are pleased to see Senators Cruz and Britt express their interest in protecting access to IVF.

View the Press Release
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Fertility and Sterility On Air - Unplugged: April 2024

Topics include: IVF in film, a rat model of fallopian tube torsion, comparing letrozole regimens for PCOS, and a review of chronic endometritis. Listen to the Episode
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ASRM Files Amicus Brief in Texas Embryo Case

ASRM has filed an amicus curiae (friend of the court) brief in the case of Antoun v Antoun, which is pending before the Texas Supreme Court. 

View the Press Release
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Financial ‘‘risk-sharing’’ or refund programs in assisted reproduction: an Ethics Committee opinion (2023)

Financial ‘‘risk-sharing’’ fee structures in programs charge patients a higher initial fee but provide reduced fees for subsequent cycles. View the Committee Document
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Survey shows strong support for increased access to fertility treatments

A new public opinion poll reveals strong support for improved access to In Vitro Fertilization (IVF). 

View the Press Release
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National Infertility Awareness Week 2024: Leave Your Mark

Next week is National Infertility Awareness Week, a federally recognized health observance founded to increase awareness of infertility.

View the Press Release
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ASRM Today: ASRM Policy Matters: Post-Alabama IVF decision advocacy roundup with Jessie Losch

Jessie Losch, ASRM Government Affairs Manager, updates ASRM Today on the advocacy efforts underway post the Alabama Supreme Court decision. Listen to the Episode
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IVF-assisted pregnancies constitute 2.5% of all births in 2022

In 2022, the number of babies born from IVF increased from 89,208 in 2021 to 91,771 in 2022. This means that 2.5% of births in the US are a result of ART.

View the Press Release
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Fertility and Sterility On Air - Live from PCRS 2024

Fertility & Sterility on Air brings you the highlights from the 2024 Annual Meeting of the Pacific Coast Reproductive Society. Listen to the Episode
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Fertility and Sterility On Air - Seminal Article: Dr. Jeremy Applebaum

Listen to this interview featuring Dr. Jeremy Applebaum, who recently published "Impact of coronavirus disease 2019 vaccination on live birth rates after IVF" Listen to the Episode
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ASRM provides testimony to Senate Judiciary Committee on threats facing IVF

ASRM shared with the Senate Judiciary Committee the dangers to reproductive medicine nearly two years after the Dobbs decision.

View the Press Release
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Fertility and Sterility On Air - TOC: March 2024

Topics this month include the impact of COVID-19 vaccination on live birth rates after IVF, the "freeze-all" strategy in women with adenomyosis, and more. Listen to the Episode
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ASRM reacts to Alabama legislation

We are pleased that the legislation passed into law by the Alabama General Assembly will at least allow our members in the state to care for their patients.

View the Press Release
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IVF at the SOTU: Fertility care expected to be major focus at State of the Union

Protecting access to IVF care is expected to be a major theme of the State of the Union on Thursday.

View the Press Release
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ASRM Responds to Proposed Alabama Legislation

We are proud of our Alabama members and their patients, who have been such incredible advocates working to motivate their legislators to protect IVF.

View the Press Release
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Senate Budget Hearing is Well Timed Following Alabama IVF Ruling

ASRM statement regarding the Senate Budget Committee’s hearing entitled: No Rights to Speak of: The Economic Harms of Restricting Reproductive Freedom.

View the Press Release
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ASRM Responds to Senate’s Failure to Pass Access to Family Building Act

We are disappointed by the Senate’s failure to meet the moment and pass federal legislation protecting access to in vitro fertilization (IVF).

View the Press Release
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Alabama Supreme Court Rules Frozen Embryos are “Unborn Children” and admonishes IVF’s “Wild West” treatment

Legally Speaking™ on presenting facts and reflecting on the impact and potential implications of  legal developments in ART. View the Column
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ASRM Condemns Profoundly Misguided and Dangerous Court Decision in Alabama

In LePage v Mobile Infirmary Clinic, the Alabama Supreme Court made a decision that flies in the face of medical reality and the needs of the citizens.

View the Press Release
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Fertility and Sterility On Air - TOC: February 2024

Topics this month include the optimial AMH level in oocyte donors, the role of mean number of DNA breakpoints (MDB) in sperm DNA integrity, and more. Listen to the Episode
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Prevention of moderate and severe ovarian hyperstimulation syndrome: a guideline (2023)

Ovarian hyperstimulation syndrome is a serious complication associatedwith assisted reproductive technology. View the guideline
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Fertility and Sterility On Air - Unplugged: January 2024

Topics this month include: HCG as a predictor of pregnancy outcome after IVF, progestin ovulation suppression and embryo development, and more. Listen to the Episode
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ASRM applauds introduction of Access to Family Building Act of 2024

ASRM is thrilled by the introduction of the Access to Family Building Act 

View the Press Release
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Billing IVF lab work

We typically bill our IVF Lab work under the rendering provider who performs the VOR. Who should be the supervising provider for embryology billing? View the Answer
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Journal Club Global: IVM in Clinical Practice: An Idea Whose Time Has Come?

In vitro maturation (IVM) has the potential to make IVF cheaper, safer, and more widely accessible to patients with infertility. View the Video
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Comparison of pregnancy rates for poor responders using IVF with mild ovarian stimulation versus conventional IVF: a guideline (2018)

Mild-stimulation protocols with in vitro fertilization (IVF) generally aim to use less medication than conventional IVF. View the Guideline
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IVF cycle management and facility fees, an overview

How should IVF Cycle Management be coded?  View the Answer
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Limited ultrasound performed by RN

Would it be appropriate to bill a 99211 when an RN is doing a limited ultrasound and documenting findings during an IUI or IVF treatment cycle? View the Answer
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CPT 89253 and 89254 for Assisted hatching

Can I bill CPT codes 89253 and 89254 together? If yes, do I need a modifier on any of the codes? View the Answer
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Journal Club Global - What is the optimal number of oocytes to reach a live-birth following IVF?

The optimal number of oocytes necessary to expect a live birth following in vitro fertilization remains unclear. View the Video
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Patient Education

What is the correct way to bill for the patient education sessions performed by registered nurses to individual patients prior to their IVF cycle? View the Answer
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Pregnancy Ultrasound

Our practice does routine ultrasounds (sac check- 76817) at the end of an IVF cycle and bill with a diagnosis code O09.081, pregnancy resulting from ART.  View the Answer
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IV Fluids During Egg Retrieval

Is it appropriate to bill the insurance company for CPT 96360, Under Hydration Infusion when being used in conjunction with IVF retrieval? View the Answer
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IUI or IVF

Should other ovarian dysfunction (diagnosis code E28.8) or unspecified ovarian dysfunction (diagnosis code E28.9) can be used for an IUI or an IVF cycle View the Answer
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IVF Case Rates

What ICD-10 codes apply to case rates? View the Answer
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IVF Consent Counseling

When a patient is scheduled to undergo IVF and the provider schedules the patient for a 30-minute consultation is this visit billable? View the Answer
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Ovulation Induction Monitoring for IUI

We would like to clarify the correct ICD 10 diagnosis code for monitoring of an IUI cycle.  View the Answer
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In Vitro Maturation

Have CPT codes been established for maturation in vitro? View the Answer
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IVF Billing Forms

I am seeking information on IVF insurance billing guidelines.  View the Answer
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IVF Billing Globally

Am I correct in assuming that it is duplicate billing for both the ambulatory center and embryology laboratory to bill globally? View the Answer
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IVF Billing of Professional Charges

Are we allowed to bill professional charges under the physician for the embryologist who performs the IVF laboratory services? View the Answer
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Lab Case Rates

What ICD-10 codes apply to case rates? View the Answer
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Oocyte Denudation

Is there is a separate code for denudation of oocytes?  View the Answer
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Endometrial Biopsy/Scratch

What CPT code should be used for a “scratch test”?  View the Answer
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Endometriosis and Infertility

For treatment like IVF would we bill with N97.x first or an endometriosis diagnosis? View the Answer
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Follicle Monitoring For Diminished Ovarian Reserve

If a patient has decreased ovarian reserve (ICD-10 E28.8) and patient is undergoing follicle tracking to undergo either an IUI cycle or IVF cycle... View the Answer
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Global Billing Vs Billing Under Provider

For an IVF cycle (that is not being billed global to an insurance plan) is it appropriate to bill the charges under one “global” provider? View the Answer
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Diagnosis of Infertility for IVF Procedure

How important is it to have accurate documentation of the type of infertility diagnosis for IVF procedures?  View the Answer
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Egg Culture and Fertilization

We are billing for the technical component of 89250 and would like to also bill a professional component of the 89250. View the Answer
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Egg Culture and Fertilization: Same Gender

A same-sex male couple requested half their donor eggs be fertilized with sperm from male #1 and the other half fertilized from male #2. View the Answer
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Donor Embryos

Could you give guidance for the correct ICD-10 code(s) to use when a patient is doing an Anonymous Donor Embryo Transfer cycle? View the Answer
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Journal Club Global: Natural versus Programmed FET Cycles

A significant portion of IVF cycles now utilize frozen embryo transfer.
View the Video
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Role of assisted hatching in in vitro fertilization: a guideline (2022)

There is moderate evidence that assisted hatching does not significantly improve live birth rates in fresh assisted reproductive technology cycles View the Committee Opinion
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Journal Club Global - Best Practices of High Performing ART Clinics

This Fertility and Sterility Journal Club Global discusses February’s seminal article, “Common practices among consistently high-performing in vitro fertilization programs in the United States: a 10 year update.” View the Video
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Guidance on the limits to the number of embryos to transfer: a committee opinion (2021)

ASRM's guidelines for the limits on the number of embryos to be transferred during IVF cycles have been further refined ... View the Committee Opinion
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Journal Club Global Live from India - Adjuvants in IVF and IVF Add-Ons for the Endometrium

Many adjuvants have been utilized by IVF centers to improve their success rates. View the Video
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Evidence-based outcomes after oocyte cryopreservation for donor oocyte in vitro fertilization and planned oocyte cryopreservation: a guideline (2021)

A review of success rates, factors that may impact success rates, and  outcomes. View the Committee Opinion
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Development of an emergency plan for in vitro fertilization programs: a committee opinion (2021)

All IVF programs and clinics should have a plan to protect fresh and cryopreserved human specimens (embryos, oocytes, sperm). View the Committee Opinion
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Fertility treatment when the prognosis is very poor or futile: an Ethics Committee opinion (2019)

The Ethics Committee recommends that in vitro fertilization (IVF) centers develop patient-centered policies regarding requests for futile treatment.  View the Committee Opinion
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Blastocyst culture and transfer in clinically assisted reproduction: a committee opinion (2018)

The purposes of this document is to review the literature regarding the clinical application of blastocyst transfer. View the Committee Opinion
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The role of immunotherapy in in vitro fertilization: a guideline (2018)

Adjuvant immunotherapy treatments in in vitro fertilization (IVF) aim to improve the outcome of assisted reproductive technology (ART) in both the general ART population as well as subgroups such as patients with recurrent miscarriage or implantation failure. View the Committee Opinion
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Performing the embryo transfer: a guideline (2017)

A systematic review of the literature was conducted which examined each of the major steps of embryo transfer. Recommendations made for improving pregnancy rates are based on interventions demonstrated to be either beneficial or not beneficial. (Fertil Steril® 2017;107:882–96. ©2017 by American Society for Reproductive Medicine.) View the Committee Guideline
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Best practices of ASRM and ESHRE: a journey through reproductive medicine (2012)

ASRM and ESHRE are the two largest societies in the world whose members comprise the major experts and professionals working in reproductive medicine. View the Committee Joint Guideline
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In Vitro Maturation Special Interest Group (IVMSIG)

IVMSIG strives to define the best strategies to optimize IVM outcomes. Learn more about IVMSIG
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What support for IVF looks like

Bipartisan support for IVF, that is responsible for the birth of over 2% of all babies born in the USA each year, will ensure that families continue to grow. View the advocacy resource
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It takes more than one

Why IVF patients often need multiple embryos to have a baby View the advocacy resource
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Oversight of IVF in the US

In the US, medical care is regulated by a complex and comprehensive network of federal and state regulations and professional oversight. View the advocacy resource
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Advocacy Resources

ASRM has prepared resources to help explain and advocate for reproductive rights and the continuation of in vitro fertilization and other fertility treatments. View the advocacy resources