Fibroids, also referred to as leiomyomas or just myomas, are regarded as non-cancerous tumors of the uterus, originating from the muscular wall. They can grow outwards protruding into the pelvic space (sub-serosal fibroid), grow inwards just under the uterine lining (submucous fibroid), protrude into the uterine cavity (intracavitary fibroid), or not protrude but remain within the uterine wall (intra-mural fibroid). Another type of fibroid is that which is attached to the uterus by a thin stalk and are referred to as “pedunculated” fibroids.

Studies have suggested that myomas are the most prevalent tumor of the uterus affecting 20%-50% of women of child-bearing age, and hence their association with infertility [1,2]. There are various ways in which fibroids may cause infertility, one of which is through compression of the fallopian tubes, leading to partial or complete obstruction to the passage of sperm or egg [3]. Other possible explanations include distortion and enlargement of the endometrial cavity by submucous and intramural categories [4,5], focal endometrial vascular disturbances, endometrial inflammation, and secretion of vasoactive substances leading to implantation failure [6,7], dysfunctional uterine contractility leading to interference with sperm and ovum transportation [6,8,9] and the possibility that intramural leiomyoma may possibly obstruct 1 or both ostia of the fallopian tubes. Previous studies reported that in approximately 5%-10% of infertile women, fibroids were found to be involved in infertility, although fibroids are found to be the single identified factor in only 1%-2.4% of infertile patients [10-14]. Substantial decreases in the levels of certain cytokines, mainly interleukin-10, and glycodelin in the mid-luteal uterine washings of women with submucosal fibroids, have been reported [15]. Glycodelin, a progesterone-regulated glycoprotein secreted into uterine cavity by secretory/decidualized endometrial glands, has characteristics of promoting angiogenesis and suppressing natural killer cells [16].

Traditional Chinese Medicine has been practiced for thousands of years. However, its recent application in the management of infertility has been controversial. Craig et al compared pregnancy rates in women who underwent fresh embryo transfer (ET) with and without 1 acupuncture session, before and after the transfer using a modified Paulus protocol, and concluded that acupuncture performed off-site on the day of ET was detrimental to the success of the transfer [17]. But others contend that luteal phase acupuncture has a positive effect on the outcome of IVF and intracytoplasmic sperm injection (ICSI) [18]. Acupuncture on the day of ET significantly improved the reproductive outcome of IVF, compared with no acupuncture treatment [19]. Others claim that acupuncture can increase blood flow to the uterus [20]. Paulus et al [21] and Magarelli et al resolved that acupuncture is a useful tool for improving pregnancy rates after Assisted reproduction Therapy (ART) and that, at specific times of IVF, it prepares the uterine lining and improves hormone levels that may also increase pregnancy rates [22]. According to Pinborg et al [23], approximately 90% of all ART cycles involve the transfer of at least 1 embryo, though only about a quarter of all cycles result in implantation of the embryo and live birth. There are various initiatives to enhance implantation rates with IVF, 1 of which is adjunct acupuncture with ET [24]. Previous work has highlighted the use of adjuvant acupuncture in ART amongst Black African women [25]. The present study reports the outcome of the application of adjunct acupuncture among 2 groups of women aged 35 years and above where 1 group was normal i.e. had no history of fibroids and thus no myomectomy, whilst the other group included those who had undergone a myomectomy to remove fibroids before their ART consultation. The main objective of this study was to evaluate whether more than 3 adjunct acupuncture sessions accompanying ET, increased the chance of pregnancy amongst older post-myomectomy women compared with normal older women without a history of fibroids.

The methods carried out in this study have previously been described [25]. In brief, this was a prospective study in female patients scheduled for IVF treatment at the Nordica Fertility Center, Nigeria, from August 1, 2016 to July 31, 2017. Signed informed consent was given before commencing the acupuncture sessions and IVF treatments. Consultants introduced the option of adjunct acupuncture therapy with their patients as part of infertility management whilst reviewing the results from the pre-IVF infertility assessment (hormonal tests and seminal fluid analysis). Inclusion criteria for study participants were (i) pre-IVF assessment, (ii) absence of any health conditions that could be adversely affected by hormonal infertility management, (iii) consent given. Exclusion criteria was no consent given. A consultant gynecologist took the relevant history from each patient such as age, occupation, marital status, number of years trying to conceive, parity and medical history of hypertension, diabetes mellitus and asthma. Patients were also asked if they had previously had IVF or acupuncture and where that had taken place. The patients’ laboratory reports suggested possible cause or causes for their infertility. Acupuncture was adjunct to IVF treatment types such as “own egg,” “recipient,” “surrogacy” and “Frozen Embryo Transfer.” After all the acupuncture sessions had been performed and at the time IVF had been completed, each woman had a 6-week ultrasound pregnancy test for confirmation. The consultant gynecologists, the embryologists and all the nursing staff were blinded to who did, or who did not receive adjunct acupuncture, and the acupuncturist was equally blind to those who received or did not receive IVF treatment. The acupuncture points used for all the patients conformed to the Chinese principles of nourishing life with acupuncture and moxibustion. Those who had more than 1 session of acupuncture before the day of ET had the following acupoints stimulated for 10 to 20 minutes: K18, CV5, CV4, CV3, ST29, LR11, KI1, SP5, GV3, GV4, BL32, and BL33. Electro acupuncture and heating lamps were used on the abdominal and back points.

On the day of ET, 2 acupuncture sessions were conducted for each patient, following the German acupuncture protocol. Before ET, the following acupoints were manually stimulated for 25-30 minutes with only the acupuncture needles: GV20 (Baihui), PC6 (Neiguan), ST29 (Guilai), SP8 (Diji), LR3 (Taichong), the right ear points Shenmen and Zhigong and the left ear points Neifenmi and Naodian. After ET, the following acupoints were manually stimulated for 25-30 minutes: LI4 (Hegu), ST36 (Zusanli), SP10 (Xuehai), SP6 (Sanyinjiao). Additional acupoints were auricular acupuncture at the following points without rotation: left ear point 55 (Shenmen), left ear point 58 (Zhigong), right ear point 22 (Neifenmi) and right ear point 34 (Naodian). Two needles were inserted in the right ear, the other 2 needles in the left ear. The 4 needles remained in the ears for 25 minutes. The side of the auricular acupuncture was changed after ET.

The procedure was carried out in a relaxed environment where it was warm and quiet, with soft music in the room. Moxibustion or cupping was not applied, neither were herbs used. All patients had the correct points needled and there were no sham treatments. The depth of the needle insertion was based on the depth of tissue. All needles used were manufactured by Beijing Zhongyan Taihe Medical Instrument Co. Ltd. Only 3 different sizes were used. These were 0.25×50, 0.25×25 and 0.18×13 for the auricular acupuncture. The same acupuncturist carried out the procedure for all the patients and the needling points were consistent with international standards. The acupuncturist received an acupuncture diploma from Beijing International Acupuncture Training Centre and had five years of experience.

Demographic and gynecologic characteristics of 75 women with impaired fertility, all ≥ 35 years old were included in the study (Table 1). Of these 75 women, 24 (32.0%) had previously undergone a myomectomy procedure for removal of fibroids (post-myomectomy group) before IVF treatment and 51 (68.0%) had no history of fibroids and therefore had no myomectomy (normal group) before IVF treatment.

There was a significant difference (t test = 2.28, p = 0.01) in the mean age of the post-myomectomy group (41.9 ± 4.5 years) compared with the normal group (39.4 ± 4.3 years). The mean BMI of post-myomectomy women (32.2 ± 7.1) was not significantly different from the normal group (30.5 ± 6.2). The majority of both the post-myomectomy women (14, 58.3%) and the normal group (24,47.1%) were obese.

The women in the post-myomectomy group had a significantly longer period of trying to conceive (10.0 ± 6.4 years) than women in the normal group (7.4 ± 55 years; (t test = 1.17, p = 0.04). Post-myomectomy women, aged ≥ 35 years, were about 5 times as likely to use a “recipient egg” rather than their “own egg” as treatment of their infertility compared with those who had no history of fibroids (χ² test = 11.88, p = 0.0006, OR = 4.85, 95% CI: 1.90, 12.38). Although post-myomectomy women had a total of 138 acupuncture sessions (Table 1, Fig. 1A) compared with 258 sessions in the normal group (Table 1, Fig. 1B), there was no significant difference (t test = 0.84, p = 0.20) in the mean number of acupuncture sessions between post-myomectomy group (5.8 ± 3.4) and the normal group (5.1 ± 3.3; Fig. 1). Only 3 (12.5%) post myomectomy patients had 1 acupuncture session compared with 9 (17.6%) of the normal group. A higher proportion (8/24, 33.3%) of post-myomectomy subjects had 10 acupuncture sessions compared with a lower proportion (12/51, 23.5%) among the normal group.

The odds ratio of post-myomectomy women becoming pregnant was 0.86 compared with the normal group [OR = 0.86, 95% CI: 0.26, 2.86 (data not shown)]. The odds ratio of post myomectomy women who had 1-3 acupuncture sessions and became pregnant was 0.44 (OR = 0.44, 95% CI: 0.04, 4.82) when compared with the normal group. However, the odds ratio of post-myomectomy women who had > 3 acupuncture sessions and became pregnant was 1.18 (OR = 1.18, 05% CI: 0.28, 4.96) when compared with the normal group. Furthermore, 3 (60.0%) of the 5 post-myomectomy women who became pregnant were obese, 1 (20.0%) was overweight and 1 was normal weight (Table 2). Fig. 2 shows the results of the pregnancy test among the 2 groups who had 1-3 or > 3 acupuncture sessions.

Not only did the proportion of pregnant, post-myomectomy patients who had received 1-3 acupuncture sessions increase from 16.7% to 22.2% with > 3 acupuncture sessions, the proportion of those who were not pregnant with 1-3 acupuncture sessions actually dropped from 83.3% to 72.2 % with > 3 acupuncture sessions. The proportion of pregnancies in the normal group following 1-3 sessions of acupuncture dropped from 26.3% to 18.7% with > 3 sessions of acupuncture, but the proportion that were not pregnant with 1-3 acupuncture sessions also dropped from 57. 9% to 18.7%.

The proportion of pregnant obese women who received 1-3 acupuncture sessions with IVF rose from 0% to 27.3% with > 3 acupuncture sessions (Fig. 3), whilst the proportion of obese women who were not pregnant and received 1-3 acupuncture sessions with IVF dropped from 100.0% to 63.6% with the administration of > 3 acupuncture sessions.

No post-myomectomy women had twin gestation but 1 (16.7%) of the 6 who had 1-3 acupuncture sessions had singleton pregnancy and 5 had negative pregnancy test or test was not done while 3 (16.7%) of the 18 who had > 3 acupuncture sessions also had a singleton pregnancy (Table 3). In contrast, only 1 (5.3%) of the 19 women in the normal group who had 1-3 acupuncture sessions had singleton pregnancy while 14 (73.7%) had negative pregnancy test or test was not done, 1 (5.3%) had missed abortion and another had ectopic pregnancy. Only 5 (15.6%) of the 32 that had > 3 acupuncture sessions had a singleton pregnancy, 26 (81.3%) had negative pregnancy test or the test was not done or there was no sac, while 1 (3.1%) had a missed abortion. The 2 women that had a twin pregnancy were in the normal group and they received just 1-3 acupuncture sessions.

Acupuncture appears to be a safe, adjunct therapy to IVF and may lead to higher pregnancy rates when used before and after ET. Pregnancy rates for women aged between 35 and 39 years and those over 40 years old were more than 10 per cent higher than in age-matched controls indicating that acupuncture may have more benefits for older women undergoing IVF [26]. In this current study, none of the patients who received acupuncture reported side effects or complications, suggesting its application with IVF is safe.

It is thought that dermal stimulation and modulation of acupuncture points, even when cursorily, modifies physiological activity. Expectancy and belief modulate the neuronal substrates of pain treated by acupuncture, not allowing sham acupuncture to be inert [27]. The majority of the meta-analyses published in 2008 were positive about the advantages of acupuncture when performed immediately prior to and immediately after ET [28] and that acupuncture improves pregnancy rates [24].

The first major issue of the current study was that post-myomectomy subjects had a higher number of acupuncture sessions than the normal group. Over the course of the study, post-myomectomy patients had 138 acupuncture sessions, a ratio of 5.8:1 or 5.8 acupuncture sessions per patient, while the normal group had 258 sessions, a ratio of 5.1:1 or approximately 5.1 acupuncture sessions per patient, although the mean number of sessions was not significantly different. The number of acupuncture sessions in this study was higher than previously reported (1 acupuncture session 25 minutes before and 25 minutes after ET [29,30], or for 25 minutes after ET [31]). The exact reason why post-myomectomy patients had more acupuncture sessions than the normal group is not clear. Probably, the acupuncturist sensed the need for more sessions among post-myomectomy subjects because of the combination of age, weight and having had fibroids. It may also be as a subjective feeling of the patients themselves. Most studies reported 1 acupuncture session just before and 1 after ET.

The second major finding was that pregnancy was documented in 4 (22.2%) out of the 18 older post-myomectomy women who had more than 3 acupuncture sessions and among only 1 (16.7%) out of the 16 subjects who had 3 or less sessions. Furthermore, the proportion of patients not pregnant dropped from 83.3% among post-myomectomy women who had 1-3 acupuncture sessions to 72.2% among those who had 3 or more sessions. Most studies report positive outcomes of acupuncture in IVF treatment [18,19,32,33], and very few studies have reported the reduction in proportion of acupuncture-treated patients who were not pregnant. It is possible that acupuncture treatment improves blood flow to the uterus [33], or it may relax the uterus around the time of ET, enhance the endometrium thickness for implantation or regulate hormones.

Lastly, the proportion of obese, older, post-myomectomy women who had more than 3 acupuncture sessions, was higher (27.3%) than that among those who had 1-3 acupuncture sessions (0.0%). This also has not been previously reported. Obesity, as with age, jeopardizes a woman’s prospect of fertility. In this current study, 3 conditions mitigated against women who had acupuncture, these were age, obesity and previous myomectomy. However, a considerable proportion of them became pregnant. This group of women may require more acupuncture sessions compared with Caucasian counterparts who are generally not as heavy.

Further research is needed to demonstrate precisely how acupuncture causes physiologic changes in the uterus and the reproductive system of Africans and Africans in diaspora.