Arch Gynecol Obstet DOI 10.1007/s00404-014-3232-6

Gynecologic Endocrinology and Reproductive Medicine

Worldwide survey of IVF practices: trigger, retrieval and embryo transfer techniques Kyle J. Tobler · Yulian Zhao · Ariel Weissman · Abha Majumdar · Milton Leong · Zeev Shoham 

Received: 6 September 2013 / Accepted: 24 March 2014 © Springer-Verlag Berlin Heidelberg 2014

Abstract  Purpose To identify common and varying practice patterns used by in vitro fertilization (IVF) providers from a broadly distributed, worldwide survey. Specific information regarding clinical IVF practices involving the oocyte maturation triggering, oocyte retrieval and embryo transfer was elicited. Methods This is an internet-based questionnaire study of IVF practices throughout the world. We used 26 multiple choice questions regarding common clinical practices. The data reported are weighted based on the number of IVF

K. J. Tobler (*) · Y. Zhao  Department of Gynecology and Obstetrics, Division of Reproductive Endocrinology and Infertility, Johns Hopkins University School of Medicine, Falls Concourse, 10751 Falls Road, Suite 280, Lutherville, MD 21093, USA e-mail: [email protected] A. Weissman  IVF Unit, Department of Obstetrics and Gynecology, Holon Sackler Faculty of Medicine, Edith Wolfson Medical Center, Tel Aviv University, Tel Aviv, Israel A. Majumdar  Center of IVF and Human Reproduction, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, India M. Leong  IVF Centre, The Hong Kong Sanatorium and Hospital, Happy Valley, Hong Kong Z. Shoham  Department of Obstetrics and Gynecology, Kaplan Medical Center, Rehovot, Israel Z. Shoham  Hebrew University of Jerusalem and Hadassah School of Medicine, Jerusalem, Israel

cycles performed at the specific IVF center, represented by a single respondent. Results  Surveys were completed from 359 centers in 71 countries throughout the world. The most common practice patterns (defined as ≥75 % of IVF cycles) identified included: use of human chorionic gonadotropin (hCG) for trigger with an antagonist protocol, no routine patient monitoring from hCG trigger to oocyte retrieval, timing oocyte retrieval 34–37 h following oocyte maturing trigger, use of a single lumen retrieval needle, no routine tests following oocyte retrieval prior to patient discharge and use of ultrasound assistance with embryo transfer. Conclusions This is the largest and most diversely represented survey of specific IVF practices addressing oocyte maturation triggers, oocyte retrieval and embryo transfers. Several uniform practice patterns were identified that can be correlated with evidence-based medicine; however, we identified multiple variable practice patterns which is likely the result of the absence of definitive evidence to guide IVF practitioners. The results of this survey allow IVF providers to compare their specific practice patterns with those of a global diverse population of IVF providers. Keywords  In vitro fertilization · Survey · Oocyte retrieval · Embryo transfer

Introduction In vitro fertilization (IVF) involves a complex series of steps including controlled ovarian hyperstimulation (COS), oocyte retrieval, fertilization, embryo culture and uterine transfer. Within each of these steps includes the potential for a wide variety of practice options. To arrive at which

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practice options lead to success, the measure and reporting of a live-born baby is considered most accurate [1]. Although many centers strictly adhere to their specific IVF protocols and report relative success, the different protocols may not be supported by definitive evidence, which establishes them as more effective over other protocols. Additionally, the process of IVF involves a significant amount of new and rapidly developing technology, including both medications and devices. The implementation and adaptation of these techniques and technologies often outpaces the ability of well-designed scientific studies capable of establishing the efficacy of certain practice modalities over others, and thus create an evidence-based standard. Despite the success reported by many centers and studies, there is currently no consistent measure of the variation in practice patters between IVF providers. The IVF-Worldwide website (www.ivf-worldwide.com) is one of the largest and most comprehensive IVF-focused website for doctors, embryologists, nurses and social workers involved in the care of IVF patients. IVF-Worldwide website links doctors and specialists from universal IVF centers to encourage dialogue, discuss special treatments and medications, and advance research on IVF issues. The website is noncommercial and has an advisory board of 52 prominent IVF clinicians and researchers [2]. Available through this website are surveys for IVF practitioners to respond regarding a range of clinical topics relevant to the practice of IVF. In this paper, we report the results of a web-based survey posted on the IVF-worldwide web site titled “Egg Collection and Embryo Transfer Techniques”. Our goal was to identify the most highly variable and the most uniformly practiced patterns from IVF clinics throughout the world involving “triggering” oocyte maturity, oocyte retrieval, and embryo transfer.

Materials and methods Johns Hopkins Institutional Review Board determined that this retrospective review qualified as exempt research under the Department of Health and Human Services regulations. This study reviews the responses to the survey titled “Egg Collection and Embryo Transfer Techniques”, posted on the website www.ivf-worldwide.com. This is a publicly accessible nonprofit website. The survey was initiated on October 17, 2010 and was closed on November 20, 2010. The questionnaire consisted of 26 multiple choice questions pertinent to IVF techniques. Two questions originally included in the survey regarding intrauterine insemination techniques were excluded from this report, since they are outside the scope of this paper. The particular focus of the survey evaluated specific preferences for the timing and

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type of oocyte maturing “trigger”, patient monitoring following the “trigger”, the timing of oocyte retrieval, varying technical aspects of the oocyte retrieval and embryo transfer procedure. In addition, specific questions regarding the logistics of patient management involved in an IVF cycle were asked. Table 1 lists the 26 survey question items. To complete the survey the practitioner’s name, the name of the IVF center they represent, email, country of IVF center and estimated total number of IVF cycles performed annually were collected. This demographic information was used to verify that only one IVF provider per center completed the survey. Computerized software assessed the self-reported demographic data to identify potential duplicate entries. Only one completed survey per IVF clinic unit was included in this review. All partially filled and duplicated surveys were excluded from our analysis. The analysis of survey responses was based on the number of IVF cycles performed by the responding IVF center. To calculate the proportion of IVF cycles represented by a particular answer, we used the total number IVF cycles for that particular multiple choice answer (center × number of annual IVF cycles) divided by total number of IVF cycles represented by all responses. Thus, the proportions reported were weighted by the number of IVF cycles represented by the particular center. A similar analysis is previously reported for a separate set of data from the IVFWorldwide.com research team [2].

Results A total of 428 centers responded to the survey, of which 69 were excluded due to incomplete responses, leaving 359 completed surveys. This survey represented a total of 71 countries and 261,300 annual IVF cycles. The US and Canada were represented by 66 of the 359 (18.4 %) centers and 35,000 IVF cycles (13.4 %). South America was represented by 42 of the 359 (11.7 %) centers and 21,400 IVF cycles (8.2 %). Europe was represented by 138 of the 359 (38.4 %) centers and 112,200 IVF cycles (42.9 %). Asia was represented by 80 of the 359 (22.3 %) centers 58,700 IVF cycles (22.5 %). Africa was represented by 18 of the 359 (5.0 %) centers and 11,100 IVF cycles (4.2 %). Australia and New Zealand were represented by 15 of the 359 (4.2 %) of centers and 22,900 IVF cycles (8.8 %). The first nine questions were asked to the respondents about their IVF clinical practice patterns regarding the use of a “trigger” for oocyte maturation. The slight majority of respondents (47 %) indicated that the optimal diameter of the leading follicle at the time of administering the “trigger” was 19–20 mm; similarly 45 % indicated an optimal diameter of 16–18 mm. Very few (6 %) indicated an optimal follicular diameter of 21–22 mm and even

Arch Gynecol Obstet Table 1  Question stems included in the survey titled “Egg Collection and Embryo Transfer Techniques” and the most reported value or practice patterns represented Question no. Question stem

Most reported value or practice (% of IVF cycles represented)

1

In your clinic, hCG is usually given when the leading follicle has reached a diameter of hCG is (usually) given when the below number of follicles reaches the optimum diameter as described above The routine dose of hCG administered in your unit is? When treating patients with GnRH antagonist during the stimulation protocol, what do you routinely use for the final stage of oocyte maturation? Do you monitor the patient again after giving the hCG and before egg retrieval? If you monitor the patient again, after hCG administration, on a routine basis, what do you look for? What is usually the time interval between hCG administration and egg collection? Is the time interval between hCG or GnRH agonist administration and egg retrieval the same? As part of the natural IVF cycle: Do you administer hCG or GnRH agonist for the final stage of oocyte maturation? What is your preferred method of analgesia/anesthesia in most cases of oocyte aspiration? What is your preference in cleansing of the vagina prior to aspiration? Which aspiration needle do you prefer to use in stimulated IVF cycles?––In most cases Do you give antibiotics following egg collection? If you give antibiotics for egg collection, usually it is given How many hours do you keep the patient under surveillance after egg collection? Before you discharge the patient from your clinic (following oocyte retrieval) do you routinely perform? Who discharges the patients from your clinic after egg collection Before transferring the embryo(s) what do you cleanse the uterine cervix with? Do you usually use a mock catheter to assess the cervical canal and uterine cavity before transferring the embryos? Do you usually perform ultrasound guided embryo transfer? Where do you place the embryos in the uterine cavity? In cases of difficult embryo transfer what measures do you take In the event that an embryo transfer is difficult we will try to solve it by While transferring the embryos do any of the following? (catheter rotational techniques) How long do you keep the patients in bed after embryo transfer?

19–20 mm (47 %); 16–18 mm (45 %)

Would you recommend some physical restriction following embryo transfer

None (32 %)

2 3 4

5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26

fewer (1 %) indicated 23–24 mm. Overall 92 % of clinics reported to give the oocyte maturing “trigger” between 16 and 20 mm, and very few people wait until follicle size is 21 mm or greater. In addition to the optimal diameter, the

3 follicles (48 %); 2 follicles (33 %) 1 ampule of Ovitrelle (46 %) hCG trigger (90 %)

No (68 %) Estrogen (8 %); progesterone (3 %); follicle size/number (6 %) 34–37 h (88 %) Yes (57 %) hCG (57 %) Light anesthesia (55 %) Saline or sterile water only (72 %) Single lumen (81 %) Yes (42 %); no or only if there is an additional indication (58 %) Single IV dose (38 %) Less than 2 h (46 %) None (84 %) Nurse (56 %) Sterile water (39 %); Media (32 %) No (64 %) Yes (77 %) Middle––halfway between internal os and fundus (56 %) Malleable stylette catheter (57 %) Cervical dilation a month prior (44 %) Leave catheter for a few seconds and rotate (36 %) None (42 %); 30–60 min (45 %)

optimal number of mature follicles with the optimal diameter at the time of the “trigger” was reported by 48 % to be at least three follicles, 33 % percent reported at least 2, 8 % reported four or more and 11 % reported at least one.

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Reporting on the type and dosage of the oocyte maturing “trigger”, the majority of respondents (46 %) reported using one ampule of choriogonadotropin alfa (Ovitrelle) equal to 6,600 IU of human chorionic gonadotropin (hCG) (Merck Serono Internal Data: Internal written communication, 20.11.2008). The next most common dose (34 %) was two ampules (10,000 IU) of urinary hCG. The least used dosages were one and a half ampules of Ovitrelle equal to 10,000 IU hCG (8 %), two ampules of Ovitrelle equal to 13,200 IU hCG (3 %) and one ampule of 5,000 IU of a urinary hCG (7 %). The survey also addressed the type of oocyte maturation “trigger” used as part of a gonadotropin-releasing hormone (GnRH) antagonist stimulation protocol. The vast majority of respondents routinely used an hCG “trigger” (90 %) over the GnRH agonist “trigger” (5 %). An additional 5 % reported the use of “none of the above”. Also inquired was if the time interval from oocyte maturation “trigger” to oocyte retrieval differed depending on whether the “trigger” used was hCG or a GnRH agonist during an GnRH antagonist protocol. The majority of respondents reported using the same time interval with 3 % reporting using a “shorter” interval and 2 % reporting a longer interval. IVF clinics were also surveyed regarding the use of additional patient monitoring in the interval of time from the administration of the oocyte maturation “trigger” to oocyte retrieval. The majority of respondents (68 %) reported not to be routinely monitoring the patients in the interval. Nine percent reported to routinely monitor, and 23 % reported to monitor only in “special cases”. Thus except for unusual circumstances, 91 % do not routinely monitor in this time interval. A follow-up question was used to inquire which variables were assessed by IVF practices that routinely monitored patients. Although 78 % responded that they do not monitor, there was an approximately even split of monitoring estrogen (8 %), progesterone (3 %), follicle size/ number (6 %) or monitoring all three variables (5 %). The optimal time interval from oocyte maturing “trigger” to oocyte retrieval was reported by the majority (88 %) as 34–37 h. The minority reported 30–34 h (4 %) and 37– 40 h (7 %). Very few (1 %) reported using a broad time range of 30–40 h. As part of a natural IVF cycle, the majority still used hCG as their “trigger” with only 1 % reporting to use a GnRH agonist; however, 3 % reported using both hCG and a GnRH agonist and 6 % reported using neither drug. Thirty-three percent reported to not perform natural IVF cycles. At the time of oocyte retrieval, the majority of respondents preferred light anesthesia (55 %) as the method of pain control. Mild sedation (i.e., diazepam given intramuscularly or intravenously) is preferred by 33 %, and local anesthesia (i.e., paracervical block) is used by 9 %. “None of

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the above” was reported by 3 %, which could have included no anesthesia for retrieval. Also at the time of oocyte retrieval, the preferred vaginal prep is sterile water or saline (72 %), followed by 15 % reporting to use antiseptic (povidone iodine) followed by irrigation with sterile water, 4 % reported to use iodine or povidone iodine without rinsing and “none of the above” was reported by 9 % of respondents. Also addressing preferred oocyte retrieval practices, the routine use of a single lumen needle at the time of oocyte retrieval was reported by 81 % of respondents and 19 % reported routine use of a double lumen needle. Two separate questions addressed the routine use of antibiotics at the time of oocyte retrieval. The majority (58 %) of responders did not routinely give antibiotics with 30 % reporting “no” and 28 % reporting only if there was an additional indication. Only 42 % routinely gave antibiotics at the time of oocyte retrieval. A second question addressed the timing of the administration of antibiotics during the oocyte retrieval and 38 % reported to give it as a single intravenous dose, 2 % reported using an intramuscular dose. A short course of oral antibiotics is routinely used by 25 % of responders and 24 % reported to not routinely use antibiotics as a response to the question regarding the timing of antibiotic administration. Following the oocyte retrieval, the majority (46 %) of respondents reported to keep the patient under observation for

Worldwide survey of IVF practices: trigger, retrieval and embryo transfer techniques.

To identify common and varying practice patterns used by in vitro fertilization (IVF) providers from a broadly distributed, worldwide survey. Specific...
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